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Anti-HIV Prenylated Flavonoids from Monotes africanus 1
Abstract
Six flavonoids, among them a new dihydroflavonol, 6,8-diprenylaromadendrin (1), and the flavonol 6,8-diprenylkaempferol (3), have been isolated from the organic extract of Monotes africanus. The isolated compounds containing a 5,7-dihydroxy-6,8-diprenyl system in the A ring of the flavonoid (1, 3, and 6) exhibited HIV-inhibitory activity in the XTT-based, whole-cell screen. In addition, several (13)C NMR assignments of lonchocarpol A (6) were corrected.
... Its HR-ESI-MS ion at m/z 423.2179 [M þ H] þ corresponds to the molecular formula of C 26 H 30 O 5 . The 1 H-and 13 C-NMR data of compound 2 were very similar to those of lonchocarpol A (Meragelman et al. 2001). The only difference is 2 containing a methoxy group in the NMR spectrum. ...
... The known compounds were elucidated as 8-prenylisosacuranetin (4) (Chen et al. 2013), lonchocarpol A (5) (Meragelman et al. 2001), 6,8-diprenylaromadendrin (Meragelman et al. 2001) (6), propolin I (7) (Huang et al. 2010), exiguaflavanone K (8) (Linuma et al. 1994), 8-prenylnarigenin (9) (Chen et al. 2013), 5,7,4 -trihydroxy-8-(2,3dihydroxy-3-methylbutyl)flavanone (10) (Cano et al. 2006), and macarecurvatin A (11) (Tanjung and Tjahjandarie 2014). Their chemical structures were determined by NMR spectra and in comparison with previously reported values. ...
... The known compounds were elucidated as 8-prenylisosacuranetin (4) (Chen et al. 2013), lonchocarpol A (5) (Meragelman et al. 2001), 6,8-diprenylaromadendrin (Meragelman et al. 2001) (6), propolin I (7) (Huang et al. 2010), exiguaflavanone K (8) (Linuma et al. 1994), 8-prenylnarigenin (9) (Chen et al. 2013), 5,7,4 -trihydroxy-8-(2,3dihydroxy-3-methylbutyl)flavanone (10) (Cano et al. 2006), and macarecurvatin A (11) (Tanjung and Tjahjandarie 2014). Their chemical structures were determined by NMR spectra and in comparison with previously reported values. ...
Two new prenylated flavonoids, 4´-methyl-8-prenyltaxifolin (1) and 6,8-diprenyl-4´-methyl-naringenin (2) and a new geranylated stilbene, 4′-deprenyl-4-methoxymappain (3) together with eight known flavonoids (4–11) were isolated from the fruits of Macaranga balansae Gagnep. Their chemical structures were determined by means of spectroscopic methods including 1D, 2D NMR, and MS data. Compound 2 showed the highest cytotoxic activity against PanC1, A549, KB and LU-1 cell lines with IC50 values range from 7.89 to 22.81 µM.
... The absorbance was read on a Thermo Scientific TM Multiskan TM FC Microplate Photometer at 405 nm. The percentage of inhibition was calculated by the following formula (Meragelman et al., 2001;Ono et al., 1990): ...
... In general, the presence of prenyl groups may increase anti-HIV activity. A flavonoid containing a 5,7-dihydroxy-6,8-diprenyl system on the A ring exhibited high anti-HIV activity (Meragelman et al., 2001;Kurapati et al., 2016). A highly active flavonoid against HIV-1 protease is 6,8-diprenylgenistein, an isoflavone with two prenyl groups on the A ring and one hydroxyl group at the 4 position of the B-ring (Lee et al., 2009). ...
Propolis (bee glue) a product of Apis mellifera L. is a resinous mixture containing chiefly beeswax and resin harvested by bees from plant leaves, buds and exudates. Extracts of a propolis sample from Salitre, a municipality of Ceará state (northeast Brazil) were obtained with solvents of increasing polarity (hexane, chloroform, ethyl acetate and methanol). A chemical profile was carried out by GC–EI-MS and HPLC–DAD–ESI-MS/MS. Lupenone, lupeol, octanoic acid tetracosyl ester and octanoic acid hexacosyl ester were identified by GC–EI-MS. Antioxidant activity was evaluated by the DPPH and β-carotene discoloring methods, and anti-HIV activity by the in vitro inhibition of HIV-1 reverse transcriptase. The ethyl acetate extract exhibited the highest antioxidant and anti-HIV activity and was fractioned by column chromatography using silica gel and seven different eluents. The active fractions were submitted to semi preparative HPLC and the following compounds were isolated: caffeic acid, p-coumaric acid, diprenylcinnamic acid, quercetin, naringenin, isorhamnetin, quercetin-3-O-diglucoside,4,2′,4′-trihydroxy-2-methoxychalcone, gossypetin-3,3′,4′,7-tetramethyl ether, myricetin-3,7,3′-trimethyl ether and 5-hydroxy-3,6,7,8,4′-pentamethoxyflavone. The ethyl acetate extract and its fractions F5-F7, as well as quercetin, isorhamnetin, myricetin-3,7,3′-trimethyl ether and p-coumaric acid exhibited high antioxidant activity on both DPPH and β-carotene antioxidant methods. Isorhamnetin exhibited moderate inhibitory effect against HIV-1 reverse transcriptase (56.99 ± 3.91%), followed by naringenin (44.22 ± 1.71%), quercetin (43.41 ± 4.56%) and diprenylcinnamic acid (41.59 ± 2.59%). These results agree with previous authors who reported anti-HIV activity of flavonoids. Keywords: Anti-HIV, Antioxidant, Brazilian propolis, Flavonoids, Botanical source, HIV-1 reverse transcriptase
... The absorbance was read on a Thermo Scientific TM Multiskan TM FC Microplate Photometer at 405 nm. The percentage of inhibition was calculated by the following formula (Meragelman et al., 2001;Ono et al., 1990): ...
... In general, the presence of prenyl groups may increase anti-HIV activity. A flavonoid containing a 5,7-dihydroxy-6,8-diprenyl system on the A ring exhibited high anti-HIV activity (Meragelman et al., 2001;Kurapati et al., 2016). A highly active flavonoid against HIV-1 protease is 6,8-diprenylgenistein, an isoflavone with two prenyl groups on the A ring and one hydroxyl group at the 4 position of the B-ring (Lee et al., 2009). ...
Propolis (bee glue) a product of Apis mellifera L. is a resinous mixture containing chiefly beeswax and resin harvested by bees from plant leaves, buds and exudates. Extracts of a propolis sample from Salitre, a municipality of Ceará state (northeast Brazil) were obtained with solvents of increasing polarity (hexane, chloroform, ethyl acetate and methanol). A chemical profile was carried out by GC–EI-MS and HPLC–DAD–ESI-MS/MS. Lupenone, lupeol, octanoic acid tetracosyl ester and octanoic acid hexacosyl ester were identified by GC–EI-MS. Antioxidant activity was evaluated by the DPPH and β-carotene discoloring methods, and anti-HIV activity by the in vitro inhibition of HIV-1 reverse transcriptase. The ethyl acetate extract exhibited the highest antioxidant and anti-HIV activity and was fractioned by column chromatography using silica gel and seven different eluents. The active fractions were submitted to semi preparative HPLC and the following compounds were isolated: caffeic acid, p-coumaric acid, diprenylcinnamic acid, quercetin, naringenin, isorhamnetin, quercetin-3-O-diglucoside,4,2′,4′-trihydroxy-2-methoxychalcone, gossypetin-3,3′,4′,7-tetramethyl ether, myricetin-3,7,3′-trimethyl ether and 5-hydroxy-3,6,7,8,4′-pentamethoxyflavone. The ethyl acetate extract and its fractions F5-F7, as well as quercetin, isorhamnetin, myricetin-3,7,3′-trimethyl ether and p-coumaric acid exhibited high antioxidant activity on both DPPH and β-carotene antioxidant methods. Isorhamnetin exhibited moderate inhibitory effect against HIV-1 reverse transcriptase (56.99 ± 3.91%), followed by naringenin (44.22 ± 1.71%), quercetin (43.41 ± 4.56%) and diprenylcinnamic acid (41.59 ± 2.59%). These results agree with previous authors who reported anti-HIV activity of flavonoids.
... However, some studies were carried out concerning the potential medicinal properties of this species. Meragelman et al. (2001) isolated flavonoids exhibiting HIV-inhibitory activity from leaf extracts of M. engleri and antifungal activity against Candida albicans was reported by Kenez et al. (2008). Table 3. Phytochemical and pharmacological studies on 12 tree species from Miombo woodlands. ...
... Particular attention should be given to species with strong potential to treat major diseases, e.g. M. engleri, B. abyssinica and P. angolensis (anti-viral) (Asres et al., 2001;Meragelman et al., 2001;Mulaudzi et al., 2013); A. senegalensis, C. zeyheri, T. stenostachya and C. spinosa (anti-tumoral) (Ahmed et al, 2010;Fyhrquist et al., 2006;Gao et al., 2010;Nibret et al., 2010); Burkea africana (glaucoma) (Dzoyem and Eloff, 2015). Attention should also be given to potentially new eco-friendly pesticides providers such as Annona senegalensis (Lame et al., 2015) and Catunaregam spinosa (Gao et al., 2011). ...
... Phenolic compounds comprise different groups including coumarins, flavonoids, tannins, naphthalenes, naphthoquinones, xanthones, lignans and alkylphenones [6]. Flavonoids and alkylphenones possess a variety of biological and pharmacological activities, including antioxidant [7], antibacterial, antiulcer [8], antifungal [9], antiviral [10], HIV -inhibiting [11], and anti-herpes simplex type 1 (HSV-1) [12]. They also inhibit electron transfer in mitochondrial inner membrane [13]. ...
... Flavonoids and alkylphenones are chemically well investigated, and a large number of member compounds have been reported. These include flavonoids and luteolin [14]; luteolin-4'-O-β-Dglucopyranoside [15]; apigenin 4-O-β-Dglucopyranoside [16]; apigenin [15]; xanhoangelol [8]; macaranggin [7]; artelastin [10]; 5,7-Dihydroxy-6,8-diphenyl flavonoids [11]; leachianone G [12] and alkylphenones such as Lalioside [17], 2,4,6-trihydroxyacetophenone-2-O-β-D-glucopyranoside [18] and lawsoniaside [19]. ...
Purpose: To examine the anti-Methods: The compounds were isolated from the leaves of Lawsonia Inermis via hyphenated high performance liquid chromatography-high resolution mass spectrometry coupled with solid phase extraction-tube transfer nuclear magnetic resonance technique. The isolated compounds were given intraperitoneally to L. tropica KWH23 amastigotes-infected albino mice at a dose of ≥ 3 mg/kg for 5 days. Amphotericin-B was used as standard (reference) drug. Lymphocytes were used to analyze their cytotoxicity. Results: For compound 1, mean lesion size decreased from 0.82 ± 0.12 to 0.10 ± 0.01 after 120 days, with 97 % cure of intracellular L. tropica amastigotes at a dose of 15 mg/kg, compared to amphotericin B which produced 95 % cure at a dose of 30 mg/kg. Half-maximal concentration (IC50) for compound 1 was 4.15 µg/ml against lymphocytes. Conclusion: The results indicate that luteolin is a potent inhibitor of L. tropica amastigotes, with a higher cytotoxic activity against lymphocytes, compared with luteolin-4'-O-β-D-glucopyranoside.
... Fifteen carbons were assigned to the flavanone skeleton, and the remaining ten carbons were ascribed to a monoterpene unit. On careful investigation, the 1 H-and 13 C-NMR spectroscopic data of 1 were quite similar to those of 6-(1,1-dimethylallyl) eriodictyol, 8) except for the added presence of a prenyl group (δ C 25.2, t, C-11; 126.5, d, C-12; 131.9, s, C-13; 25.9, q, C-14; 17.7, q, C-15). The HMBC correlations from H-10 (δ H 1.94, m; 1.72, m) to C-11 and C-12, from H-11 (δ H 1.85, m; 1.80, m) to C-10 (δ C 41.8), and from H-12 (δ H 4.99, overlapped) to C-14 and C-15, combined with one H-atom spin system (H-10/H-11/H-12) deduced from the 1 H-1 H COSY correlations, suggested that the prenyl group was attached to a methyl of the 1,1-dimethylallyl group. ...
... The relative configuration of H-2 was determined by comparing the chemical shifts and the coupling constants of H-2 and H-3 of 1 with those of 6-(1,1-dimethylallyl) eriodictyol. [8][9][10][11] And the absolute configuration at stereogenic center C-2 could be determined using circular dichroism (CD) spectroscopic analysis. Compound 1 depicted a negative Cotton effect originating from a π π* transition at 290 nm, and this was adequately indicative of a 2S configuration. ...
Two new [neougonins A (1) and B (2)] and nine known prenylated flavonoids were isolated from the whole plants of Helminthostachys zeylanica. The structures of the new isolates were elucidated by extensive NMR techniques, including one and two dimensional (1D)- and (2D)-NMR experiments, as well as comparison with spectroscopic data of known analogous compounds. Moreover, compound 1 inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells with an IC50 value of 3.32 µM.
... Recently, different isoprenylated phenols have been reported to exhibit antifungal [14], antitumor [15], anti-HIV [16], antioxidant [17], and anti-Alzheimer activities [18,19]. Additionally, isoprenylated dimethyl-benzopyranes have exhibited a wide spectrum of biological activities [20]. ...
... Ten reactions (1 mL final volume) were conducted keeping geraniol equivalents constant and varying the amount of reagents and substrates as shown in Table 3 (direct path, entries [11][12][13][14][15][16][17][18] and (stepwise path, entries [19][20]. To a solution of p-methoxyphenol 1 or ortho-monoalkylated 4-methoxyphenol in toluene at 0 • C, BF 3 ·Et 2 O (10 % in anhydrous toluene) was added followed by addition of geraniol 2. The reaction mixture was continuously stirred at 4 • C overnight and the reagents were quenched with H 2 O (3 mL) and NaHCO 3 5 % (1 mL). ...
A diversity-oriented approach for the synthesis of various structurally different prenylated alcohols from readily accessible and common precursors was developed. With varying approaches, this article describes some successful examples of a Friedel–Crafts alkylation using methoxyphenols and different prenyl alcohols (geraniol and (E,E)-farnesol). We demonstrated that just by varying the stoichiometry of the Lewis acid used, the course of the reaction can be shifted to produce the alkylated or the cyclized product. Eighteen unique products were obtained with good isolated yields by direct alkylation with or without a consecutive (Formula presented.)-cationic cyclization.
... M. africanus A.DC belongs to the Dipterocarpaceae family, and is usually a small tree of 8 m high with simple concolorous leaves. M. africanus A.DC is reported to have anti-HIV effects [26]. ...
This study evaluated the phytochemical composition and antioxidant activity of Piliostigma thonningii (Schumach.) Milne-Redh, Psorospermum febrifugum Spach, Inula glomerata Oliv. and Hiern, Zanthoxylum chalybeum Engl. and Monotes africanus A.DC., claimed to treat cancer by Malawian traditional herbal practitioners. Ground and dried plant extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC), total alkaloid content (TAC), ferric reducing antioxidant power (FRAP) and 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) using standard assays. The TPC, TFC, and TAC ranged from 539 ± 2.70 to 4602 ± 32 mg GAE/g DW, 6.18 ± 0.03 to 64.04 ± 0.16 mg QE/g DW and 19.25 ± 0.07 to 76.05 ± 0.36 mg CE/g DW, respectively, and the variations were significant, p < 0.05. FRAP values ranged from 82.15 ± 0.7 to 687.28 ± 0.71 mg TEAC/g DW and decreased in the following order: P. thoningii (Schumach.) Milne-Redh > P. febrifugum Spach > M. africanus A.DC > Z. chalybeum Engl > I. glomerata Oliv. and Hiern. The scavenging activity (SA 50) of the extracts ranged from 0.09 ± 0.01 to 1.57 ± 0.01 µg/mL of extract with P. thonningii (Schumach.) Milne-Redh showing the lowest value. Based on the levels of phenolic compounds and their antioxidant activity, the plants in this study could be considered for use as medicinal agents and sources of natural bioactive compounds and antioxidants.
... Whereas, 6-octadecanoic acid and 11-octadecanoic acid which are stearic acid has been reported to posses antibacterial, anti-oxidant, antitumor, cancer preventive, immunostimulant and chemo preventive [39]. Other compounds identified in Vernonia cinerea have been reported to posses anti-inflammatory, antioxidant, nematicide, pesticide, lubricant, antiandrogenic and haemolytic activity [40]. Pentanoic acid (8.1%) according to [41], posses antioxidant activity and anti-inflammatory. ...
The present study deals with the investigation of bioactive components in four selected medicinal plants identified in Ebonyi State Nigeria using GC/MS. The fresh leaves of Dodder esculenta, Vernonia cinerea, Erythrina senegalensis and Blighia unijugata were collected and dried in Biotechnology laboratory, Ebonyi State University, Abakaliki at room temperature, for two weeks and the dried leaves were grinded into fine powder using mechanical blender and further sieved with 2mm size sieve. This was further extracted with methanol and used for phytochemical identification by GC-MS analysis. The result revealed the presence of the following phytochemicals: fifteen in Erithrina senegalensis, eleven in Dodder esculanta, eight in Blighia unijugata, and seven in Vernonia cinerea respectively. Thus, our results revealed that the selected plants possess important phytocomponents such as nonadecenoic acid hexadecanoic acid, n-pentytacetate, and methyl caprate. Medicinal use of these plants may be attributed to these bioactive components.
... In addition, scientific consistency of all medicinal uses is supported by numerous studies highlighting the anticancer [10], antihypertensive, antidiabetic [11], antiinflammatory, antiplasmodial [12], antibacterial [13,14], anti-HIV [15], antiparasitic [16], antioxidant [17,18] and enzyme inhibitory [19,20] properties of extracts and/or secondary metabolites isolated from this plant. Similar broad range of pharmacological activities has been observed with respect to the Mimosa genus [21,22]. ...
Although Erythrina senegalensis is a plant widely used in traditional medicine in sub-Saharan Africa, its biological properties have been poorly investigated to date. We first characterized by conventional reactions the composition of several stem bark extracts and evaluated in acellular and cellular assays their pro- or antioxidant properties supported by their high phenolic and flavonoid content, particularly with the methanolic extract. The pro- or antioxidant effects observed did not correlate with their IC50 concentrations against five cancer cell lines determined by MTT assay. Indeed, the CH2Cl2 extract and its ethyl acetate (EtOAc) subfraction appeared more potent although they harbored lower pro- or antioxidant effects. Nevertheless, at equipotent concentration, both extracts induced ER- and mitochondria-derived vacuoles observed by fluorescent microscopy that further led to non-apoptotic cell death. LC coupled to high resolution MS investigations have been performed to identify chemical compounds of the extracts. These investigations highlighted the presence of compounds formerly isolated from E. senegalensis including senegalensein that could be retrieved only in the EtOAc subfraction but also thirteen other compounds, such as 16:3-Glc-stigmasterol and hexadecanoic acid, whose anticancer properties have been previously reported. Nineteen other compounds remain to be identified. In conclusion, E. senegalensis appeared rich in compounds with antioxidant and anticancer properties, supporting its use in traditional practice and its status as a species of interest for further investigations in anticancer drug research.
... Using the latter test, it has been shown that quercetin of a Brazilian propolis at 200 µg/mL induced activity against HIV-1 inhibition (Silva et al., 2019). The presence of prenyl groups on flavonoids may increase their anti-HIV activity (Kurapati et al., 2015;Meragelman et al., 2001). ...
Background
Polyphenols and particularly flavonoids are of constant interest to the scientific community. Flavonoids are investigated for their biological and pharmacological purposes, notably as antioxidant, anticancer, antiviral and for their anti-inflammatory activities. Certainly, one of the best-known flavonols recognized for its therapeutic and preventive properties, is quercetin. Despite its biological interest, quercetin suffer from some drawbacks, mainly related to its bioavailability. Hence, its synthetic or biosynthetic derivatives have been the subject of intensive research. The health-promoting biological activities of flavonols and derivatives mainly arise from their capacity to disrupt the host-pathogen interactions and/or to regulate host cellular functions including oxidative processes and immunological responses. In the age of coronavirus pandemic, the anti-inflammatory and antiviral potential of flavonols should be put forward to explore these substances for decreasing the viral load and inflammatory storm caused by the infection.
Purpose of study
The present review will decipher and discuss the antioxidant, anti-inflammatory and antiviral capacities of major flavonol with a focus on the molecular basis and structure-activity relationships.
Study design
Current study used a combination of quercetin derivatives, pathway, antioxidant, anti-inflammatory, antiviral activities as keywords to retrieve the literature. This study critically reviewed the current literature and presented the ability of natural analogs of quercetin having superior antioxidant, anti-inflammatory and antiviral effects than the original molecule.
Results
This review allowed the identification of relevant key structure-activity relationship elements and highlight approaches on the mechanisms governing the antioxidant, antiviral and anti-inflammatory activities.
Conclusion
Through a critical analysis of the literature, flavonols and more precisely quercetin derivatives reviewed and found to act simultaneously on inflammation, virus and oxidative stress, three key factors that may lead to life threatening diseases.
... 2,[3][4][5][6] Previous scientific studies have shown biological activities possessed by this plant such as antimicrobial, antidiabetic, antioxidant, analgesic, anti-inflammatory, antiviral, antimalarial and antitumor. 2,[7][8][9][10] The reported constituents of E. senegalensis are mainly phenolic compounds and prenylated flavonoids such as erythrinasinate, octacosyl (E)-fenilate, auriculatin, 2,3-dihydroauriculation, lonchocarpol A, scandenone, erysenegalensein D-M, 4 ′ ,5,7-trihydroxy-6,8-diprenylisoflavone, 6,8-diprenylgenistein, alpumisoflavone, 2,3,11,12 , and alkaloids such as erysocline, erysopine, erysotrine, erythratidine, 11-hydroxyerysodine, 11-hydroxyerysovine, 11-oxyerysodine and glucoerysodine. 2,13,14 There are many documented medicinal benefits of Erythrina senegalensis, and, thereby, it is necessary to investigate scientifically the chemical compounds contained in this plant, as well as their biological activities. ...
Phytochemical study of the roots of Erythrina senegalensis led to the isolation of a new α-sophoradiol glycoside, erythrinoside (1), together with four known compounds, lupeol (2), α-sophoradiol (3), isoneorautenol (4) and D-mannitol (5). The structures of the compounds were elucidated using spectroscopic data including 1D and 2D NMR, mass spectrometry and by comparison made with some data reported previously; the samples (extracts and compounds) were also subjected to antidiabetic assay. Erythrinoside and isoneorautenol exhibited good α-amylase inhibitory potential of 54.6% and 53.3%, respectively, compared to acar-bose (72.5%) at 400 µg/mL. With α-glucosidase, all samples showed promising inhibition percentages above 50% at 200 µg/mL. In the α-glucosidase assay, the ethyl acetate extract (65.5%), methanol extract (72.1%), erythrinoside (63.3%) and isoneorautenol (66.0%) had percentage inhibitions closer to that of acarbose (69.0%) at 200 µg/mL. The methanol extract (IC 50 = 81.2 ± 0.9 µg/mL) was more active than acarbose (IC 50 = 94.5 ± 0.7 µg.mL) in the α-glucosidase assay. The inhibition of α-amylase and α-glucosidase indicates that E. senegalensis extracts and compounds could be used to manage diabetic conditions.
... Within flavonoids, the following compounds were analysed regarding anti-HIV activity: -prenylated flavonoids, namely: 6,8-diprenylaromadendrin (fig. 1, compound 1) and 6,8-diprenylkaempferol (fig. 1, compound 2), isolated from Monotes africanus A. DC. The compounds showed HIV inhibitory effects in the XTT-based, whole cell screen test[5,6]; -quercetin 3-O-(2'-galloyl)-α -L-arabinopyranoside (fig. 1, compound 3)isolated from Acer okamotoanum Nakai, exhibited anti-HIV-1 integrase activity[7]; -biflavonoids (dimeric flavonoids), namely: robustaflavone (C3'-C6" linkage flavonol) (fig. 1, compound 4) and hinokiflavone (C4'-O-C6" linked flavonol) (fig. 1, compound 5) isolated from Rhus succedanea (L.) Kuntze., demonstrated activity against HIV-1 reverse transcriptase (RTase) in in vitro tests[8]; ...
Acquired immunodeficiency syndrome (AIDS) is an immunosuppressive disease caused by human immunodeficiency virus (HIV). The urgent need for searching novel anti-HIV/AIDS medicines is a global concern. So far, a lot of medicinal and aromatic plants (MAPs) have been analyzed to select those that could assist in the prevention and/or amelioration of the disease. Among biologically active compounds present in these plants, one of the most promising group are phenolics. The purpose of this article was to report anti-HIV activity of selected phenolic compounds of plant origin.
... The anti-HIV prenylated flavonoids as 6, 8-diprenylaromadendrin, 6, 8-diprenylkaempferol and lonchocarpol an isolated from the plant Monotes africanus exhibited HIV-inhibitory activity in the XTT-based, whole-cell screen. (Meragelman et al., 2001). Ixeris chinensis Nakai (Compositae) known as Siyekucai, is a perennial plant, and used as a folk medicine in China for the treatment of bronchitis, pneumonia, pharyngitis, dysentery and poisonous indigestion on the basis of its anti-febrile, antidotal and analgesic effects (Shiojima et al., 1996). ...
The word phytopharmaceutical deals with a complex mixture of compounds derived from the plant source that is used as a medicine or drug. Primitive human societies have been depending on plants and plant products for various remedies. Several plants in the different forms have been reported in traditional medicine and to find a rational for the treatment of various diseases than to isolated single compounds. Many of the single compounds isolated from the plant origin are effectively used in the medicine. The search of natural products in drug discovery has been greatly enhanced in the last few years. The impetus to use phytopharmaceutical agents for the treatment of disease, most of the plant based drugs are quite safe and have lesser adverse effects and are claimed that it works as synergistic effects.
... Author Copy Non Commercial Use Lanostane-type triterpene is a suberosol that can be obtained from leaves and stems of Polyalthia suberosa; and it has exhibited inhibitory activity on HIV replication in H9 cells. Triterpene lactone (lanci lactone C extracted from roots and stems of Kadsuralancilimba) may restrain HIV replication in veteran cells [50]. TPA (12-O-tetra-decanoylphorbol-13-acetate) is a phorboldi ester and is obtained with methanolic extract from Croton tiglium; and it shows inhibitory activity on cytopathogenic effects of HIV-1. ...
The catastrophic rise in numeral of individuals suffered from human immunodeficiency virus (HIV)/Acquired immunodeficiency syndrome (AIDS) has necessitated global concern for finding an effective solution to prevent HIV infection. Though the combination antiretroviral therapy (cART) is effective in regards to prevention of HIV proliferation, which doesn’t deprive of from adverse consequences, which multiply over the life long treatment. Moreover, the emergence of drug resistance limits the cART, and hence novel drugs as well as newer objects are the necessity of the epoch have to worked upon. In this pursuance, the research for the drugs that attack HIV reservoirs, like brain, lymph nodes, blood, and digestive tract, has shifted our focus towards plant metabolites, like coumarins, terpenes, flavonoids, alkaloids, phenolics, lignans, quinones, saponins, etc. These metabolites have shown promising anti-HIV and neuroprotective properties. The present chapter focuses on biodiversity of flora monarchy as well as presents an overview of the potential of such plant extracts against HIV/AIDS along with their function in relation of HIV-associated neurocognitive disorders (HAND).
... The flavonoid moiety (4H-chromen-4-one) is known to be mainly responsible for the therapeutic activity, while glycosidic portion attached to the flavonoid enhances the solubility of the compounds and thus boosts its therapeutic activity. Two flavonoids 6,8-diprenylkaempferol and 6,8-diprenylaromadendrin isolated from Monotes africanus have expressed potential activity against the AIDS virus [281]. Another anti-HIV biflavonoid named wikstrol B (67) (Figure 14) has been isolated from Wikstroemia indica (Thymelaeaceae) roots [282]. ...
Acquired Immunodeficiency Syndrome (AIDS), which chiefly originatesfroma retrovirus named Human Immunodeficiency Virus (HIV), has impacted about 70 million people worldwide. Even though several advances have been made in the field of antiretroviral combination therapy, HIV is still responsible for a considerable number of deaths in Africa. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. Presently, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate drugs derived from plants as well as their derivatives. Several plants, such as Andrographis paniculata,Dioscorea bulbifera,Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity.Here, weattempt to summarize the main results, which focus on the structures of most potent plant-based natural products having anti-HIV activity along with their mechanisms of action and IC50 values, structure-activity-relationships and important key findings.
... Flavonoids seized the attraction of chemists worldwide as its varied derivatives exhibit an array of pharmacological activities. The most promising pharmacological activities include antibacterial [3], antifungal [4], antimalarial [5], anticancer [6] antioxidant [7], antidiabetic [8], anti-HIV [9], anti-tubercular [10], anti-inflammatory [11], immune-stimulatory [12], and wound healing [13] as shown in (Fig. 1). ...
A mild and efficient scheme for the synthesis of 3-substituted functionalized flavones was developed. The reaction of flavanone and glyoxylic acid in ethanol in the presence of the catalytic amount of sulphuric acid at reflux temperature for 2–3 h yielded good to excellent functionalized flavones. As per present scenario for the synthesis of different substituted flavones, this method represents mild reaction conditions, low-cost catalyst, broad substrate scope along with high yields, which makes it more credible and handy synthetic strategy.
... 2. On a isolé chez cette espèce des flavonoïdes actifs contre le virus HIV (Meragelman & al. 2001). ...
A flora treatment for the Dipterocarpaceae occurring in the Democratic Republic of the Congo, Rwanda and Burundi is given. In this region, the family is represented by two genera and fifteen species. Within these species one subspecies, 16 varieties and 8 formae have been distinguished. The taxonomic status of three taxa is doubtfull and these are treated as insufficiently known. User-friendly keys to all taxa are included. Seven taxa are endemic to the area, and many others appear to be rare. All species come with a full description, synonyms, data on their distribution, habitat, vernacular names and uses, as well as references to additional literature and the citation of representative specimens used. Three species are illustrated with drawings and 13 with colour photographs.
... Values are given as the mean ± SD from three independent experiments. (7), 27 tonkinochromane G (8), 24 sophoranochromene (9), 24 5-dehydroxylupinifolin (10), 28 sophoradin (11), 29 6,8-diprenylkaempferol (12), 30 tonkinensisol (13), 31 and medicarpin (14) 32 were identified by comparison with published data. ...
Neuroinflammation underlies many neuro-degenerative diseases. In this paper, we report the identification of a new pterocarpan-type anti-inflammatory compound named sophotokin isolated from Sophora tonkinensis. S. tonkinensis has been used traditionally for treatment of conditions related to inflammation. Our initial screening showed that sophotokin dose-dependently inhibits lipopolysaccharide (LPS)-stimulated production of NO, TNF-α, PGE2 and IL-1β in microglial cells. This anti-neuroinflammatory effect was associated with sophotokin’s blockade of LPS-induced production of the inflammatory mediators iNOS and COX-2. Western blot and qPCR analysis demonstrated that sophotokin inhibits both the p38-MAPK and NF-κB signal pathways. Further studies revealed that sophotokin also suppresses the expression of cluster differentiation 14 (CD14) in the toll-like receptor 4 (TLR4) signaling pathway. Following down-regulation of MyD88 and TRAF6, sophotokin inhibits the activation of the NF-κB and MAPK signal pathways in LPS-induced BV-2 cells. In silico studies suggested that sophotokin could interact with PU.1-DNA complex through hydrogen binding at sites 1 and 2 of the complex, blocking the DNA binding. This suggests that PU.1 may be a potential target of sophotokin. Taken together, these results suggest that sophotokin may have therapeutic potential for diseases related to neuroinflammation. The mechanism of anti-neuroinflammatory effects involves inhibition of the TLR4 signal pathway at the sites of NF-κB and MAPK with PU.1 as a likely upstream target.
... Some species of the families Malvaceae, Bombacaceae, Sterculiaceae and Thymelaeaceae are also characterized by flavone C-glycosides and flavone O-C-diglycosides similar to Neurada ( Giannasi, 1988;Seetharaman, 1990;Faizi and Ali, 1996;Joshi et al., 2013). Within the expanded Malvales, genus Momobtes (family Dipterocarpaceae) and genus Cochlospermum (family Bixaceae) show a similarity to Neurada in the presence of dihydroflavonols and their glycosides ( Meragelman et al., 2001;Solon et al., 2012). Finally, also both genera Neurada and Momobtes are characterized by oblate pollen in a recent study ( Polevova et al., 2010). ...
Seven flavonoids; taxifolin (1), taxifolin 3-O-β-rhamnopyranoside (2), vitexin (3), vitexin 2'-O-α-rhamnopyranoside (4), orientin 2'-O-α- rhamnopyranoside (5) and isoorientin 2'-O-α-rhamnopyranoside (6), p-hydroxybenzoic acid (7) have been isolated from the whole plant of Neurada procumbens L. Antioxidant and cytotoxicity properties of the methanol and water extracts were investigated. The chemotaxonomic significance was also investigated.
... et al., 2014), trifolirhizin 6 -monoacetate (4; Yang X.Z. et al., 2014), quercetin (5; Yi et al., 2002), lespeflorin B4 (7; Mori-Hongo et al., 2009), dehydrolupinifolinol (8; Sutthivaiyakit et al., 2009), glabrol (9; Cho et al., 2012), euchrenone a2 (11;Mizuno et al., 1988), 6,8-diprenylkaempferol (12;Meragelman et al., 2001), and sophoranochromene (13;Li et al., 2008) by comparison with their mass spectrum (MS), UV, and NMR spectra with published reference data. Spectroscopic data of compounds 1-13 could be found in S2 in Supplementary Material. ...
This study investigated the active principles, hypoglycemic activity and potential mechanisms of the flavonoid rich extract from Sophora tonkinensis Gagnep. (ST-EtOAc) in KK-Ay diabetic mice. An off-line semipreparative liquid chromatography-nuclear magnetic resonance (LC-NMR) and liquid chromatography-ultraviolet-electrospray ionization mass spectrometry (LC-UV–ESIMS) protocol was performed to determine 13 flavonoids from ST-EtOAc. ST-EtOAc administrated orally to the KK-Ay mice significantly increased their sensibility to insulin, reduced fasting blood-glucose levels and blood lipid indexes such as triglyceride and cholesterol. Moreover, ST-EtOAc exhibited a strong effect of stimulation on glucose transporter 4 (GLUT4) translocation by 2.7-fold in L6 cells. However, the selective AMP-activated protein kinase (AMPK) inhibitor compound C can completely inhibit the activation of the AMPK pathway and prevent the GLUT4 translocation caused by ST-EtOAc. In vivo, phosphorylation of the AMPK expression in the liver and skeletal muscle was measured. The results showed phosphorylation of the AMPK had been improved and GLUT4 expression had been also enhanced. In this paper, we conclude that, ST-EtOAc seems to have potential beneficial effects on the treatment of type 2 diabetes mellitus with the probable mechanism of stimulating GLUT4 translocation modulated by the AMPK pathway.
... In our previous reports, we disclosed the presence of isoprenylated and geranylated flavonoids [1][2][3][4], and phenolic derivatives containing an irregular sesquiterpenyl side chain, from Indonesian Macaranga [3,5]. In continuation of these chemical investigations, we have examined M. recurvata Gage and succeeded in isolating two new dihydroflavonols, trivially named as macarecurvatins A (1) and B (2), together with the known compounds 6,8-diisoprenylaromadendrin (3) [6], glyasperin A (4) [7], and broussoflavonol F (5) [8]. This paper discusses the structure elucidation of the new compounds. ...
... Baicalin (Figure 1) inhibits HIV replication in PBMC in a dose dependent fashion and is an anti-HIV flavonoid extracted from Scutellaria baicalensis (Ohtake et al., 2004). The 6,8-diprenylaromadendrin and 6,8-diprenylkaempferol, prenylated flavonoids, also show anti-HIV activity in the XTT-based, whole-cell screen and are derived from the extract of Monotes africanus (Meragelman et al., 2001). Flavonoid gallate ester and quercetin 3-O-(2galloyl) a-L-arbinopyranose can inhibit integrase activity of HIV-1 and are obtained from ethanolic extract of Acer okamotoanum from the Aceraceae family . ...
As the threat of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) persists to rise, effective drug treatments are required to treat the infected people. Even though combination antiretroviral therapy (cART) provides stable viral suppression, it is not devoid of undesirable side effects, especially in persons undergoing long-term treatment. The present therapy finds its limitations in the emergence of multidrug resistance and accordingly finding new drugs and novel targets is the need of the hour to treat the infected persons and further to attack HIV reservoirs in the body like brain, lymph nodes to achieve the ultimate goal of complete eradication of HIV and AIDS. Natural products such as plant-originated compounds and plant extracts have enormous potential to become drug leads with anti-HIV and neuroprotective activity. Accordingly, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action and for HIV-associated neurocognitive disorders (HAND). The basic challenge that still persists is to develop viral replication-targeted therapy using novel anti-HIV compounds with new mode of action, accepted toxicity and less resistance profile. Against this backdrop, the World Health Organization (WHO) suggested the need to evaluate ethno-medicines for the management of HIV/AIDS. Consequently, there is need to evaluate traditional medicine, particularly medicinal plants and other natural products that may yield effective and affordable therapeutic agents. Although there are a good number of reports on traditional uses of plants to treat various diseases, knowledge of herbal remedies used to manage HIV/AIDS and HAND are scanty, vague and not well documented. In this review, plant substances showing a promising action that is anti-HIV and HAND will be explored along with what they interact. Since some plant substances are also known to modulate several cellular factors which are also involved in the replication of HIV and hence their role as potential candidates will be discussed. HIV/AIDS being an exceptional epidemic, demands an exceptional approach and that forms very much focus for the current review.
... Ce composé inhibe de manière significative à la fois COX-1 et COX-2 et prévient les lésions prénéoplasiques mammaires induites par le 7,12-diméthylbenz(Į)anthracène (DMBA) (Jang et al., 2002). Il possède une action antivirale contre VIH-1 (Meragelman et al., 2001). Le lonchocarpol A est capable d'inhiber la synthèse macromoléculaire de Bacillus megaterium (Salvatore et al., 1998), par contre il n'a aucune activité contre Candida albicans (Garo et al., 1998). ...
Plants of the genus Derris (Fabaceae)are known to contain flavonoids particularly isoflavonoids such as rotenoids. Derris ferruginea (Benth.), originate to Asia, is traditionally used as insecticide, fish poison and in the fight against ectoparasites. Phytochemical study of extracts from stems and leaves of Derris ferruginea were made to isolate and characterize 14 compounds mainly flavanones and isoflavonoids. Almost of them are prenylated. An extended biological evaluation was performed for crude extracts and some isolated compounds. Alternatives methods were developed to obtain two interesting compounds. Centrifugal partition chromatography has resulted in purification in larger amounts of cajaflavanone which possess intersting properties in terms of biological ( anti-inflammatory effect on microglia1 cells, inhibiting the formation of advanced glycation and products by a non-antioxidant mechanism, proangiogenic / effect ex vivo). The synthesis of a novel compound was undertaken and permitted to validate its structure. Finally, the major compound of the leaf was preliminary tested on a model to study its insecticidal activity: the DUM neurons of Periplaneta americana. This electrophysiological technique allows understanding the mechanism of action of this compound.
... From the three Cameroon samples thirteen triterpenoids were isolated: lupenone (1), β-amyrin (2), ψ-taraxasterol-acetate (6), taraxasterol acetate (7), lupeol acetate (8), lanosterol (9) 3α-hydroxy-olean-12-en-30-ol (10), α-amyrone (11), α-amyrin (12) β-acetoxy-amyrin (15), bacchara12,21dien3β-ol (16), betulinaldehyde (17), and erythrodiol (18), together with two monoterpene alcohols: α-terpineol (13) and 1, 8-terpineol (14), one fatty acid ester: ethyl palmitate (21), and three diprenyl-flavonoids: lonchocarpol A (4), 6,8-diprenyl-aromadendrin (19) and lespedezaflavanone C (20). The metabolites were identified by a combination of spectroscopic (1D and 2D NMR) and mass spectrometric techniques and comparison with literature data [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. According to published studies on Cameroon propolis [4a-d] it is clearly proved that it is rich in pentacyclic triterpenes and especially in derivatives of lupeol and amyrin. ...
The objective of this study was the chemical analysis of four selected samples of African propolis (Congo and Cameroon) and their biological evaluation. Twenty-one secondary metabolites belonging to four different chemical groups were isolated from the 70% ethanolic extracts of propolis and their structures were elucidated on the basis of spectral evidence. Three triterpenes and two diprenyl-flavonoids were identified from Congo propolis, which has been investigated for the first time, while thirteen triterpenes, three diprenyl-flavonoids, two monoterpenic alcohols and one fatty acid ester have been identified from Cameroon propolis samples. To our knowledge, the identified diprenyl-flavonoids, as well as five of the isolated and determined triterpenes, are reported for the first time in propolis. Moreover, the total polyphenol content was estimated in all extracts and the antimicrobial activities of all four extracts were studied against six Gram-positive and -negative bacteria and three pathogenic fungi, showing an interesting antibacterial profile.
Four undescribed prenylated flavonoids, sophoratones A–D (1‐4), and 17 known flavonoids, were obtained from the aerial parts of Sophora tonkinensis. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and ECD calculations. Meanwhile, the ability of these compounds to inhibit the release of nitric oxide (NO) by a lipopolysaccharide induced mouse in RAW 264.7 cells was assayed. The results indicated that some compounds exhibited clear inhibitory effects, with IC50 ranging from 19.91 ± 1.08 to 35.72 ± 2.92 µM. These results suggest that prenylated flavonoids from the aerial parts of S. tonkinensis could potentially be used as a latent source of anti‐inflammatory agents.
Introduction: Propolis is a resinous natural substance collected by honeybees from
buds and exudates of various trees and plants; it is widely accepted that the composi�tion of propolis depends on the phytogeographic characteristics of the site of collection.
Objectives: The aim of this study was to determine the phytochemical composition
of ethanolic extracts from eight propolis batches collected in different regions of
Benin (north, center, and south) and Congo, Africa.
Material and methods: Characterization of propolis samples was performed by using
different hyphenated chromatographic methods combined with carbon-13 nuclear
magnetic resonance (13C NMR) dereplication with MixONat software. Their antioxi�dant or anti-advanced glycation end-product (anti-AGE) activity was then evaluated by using diphenylpicrylhydrazyl and bovine serum albumin assays, respectively.
Results: Chromatographic analyses combined with 13C NMR dereplication showed
that two samples from the center of Benin exhibited, in addition to a huge amount of
pentacyclic triterpenes, methoxylated stilbenoids or phenanthrenoids, responsible for the antioxidant activity of the extract for the first one. Among them, combretastatins might be cytotoxic. For the second one, the prenylated flavanones known in Macaranga-type propolis were responsible for its significant anti-AGE activity. The sample from Congo was composed of many triterpene derivatives belonging to Mangifera indica species.
Conclusion: Therefore, propolis from the center of Benin seems to be of particular
interest, due to its antioxidant and anti-AGE properties. Nevertheless, as standardization of propolis is difficult in tropical zones due to its great chemodiversity, a system�atic phytochemical analysis is required before promoting the use of propolis in food and health products in Africa
Infectious diseases accounts for approximately one-half of deaths that occurs in tropical countries including Malawi and majority of people in these countries use traditional medicine for PHC. Therefore, the purpose of the present study was to investigate the antimycobacterial and antiviral activities of extracts and compounds isolated from Aeschynomene nyassana, Euphoria whyteana, Euphobia cooperi, Flueggea virosa, Phyllanthus amarus, Ericae milanjiana and Rhus acuminatissima medicinal plants. Ethnobotanical survey was conducted in order to identify the selected medicinal plants and these were extracted twice with solvents MeOH, EtOAc, Hex and DCM. Part of the MeOH/H2O extracts obtained was subjected to alkaloid extraction scheme while the other part to column chromatograph. LCMS and Nmr were used to identify and elucidate the structures. Phytochemical screening was done in order to identify Phytochemical compounds and drug susceptibility against MDR-TB was performed using BACTEC MGIT 320 system. Cell viability and cytotoxicity studies were performed using Trypsin blue dye exclusion, MTT and macrophage Raw 264.7 cell assays while heavy metal analysis was done using AAS. The results of M. smegmatis showed that F. virosa and E. milanjiana crude extracts had Mic of 128 ug/ml and 512 ug/ml respectively while E. cooperi, E. milanjiana and E. whyteana crude extracts had MIC of 512 mg/ml and E. whyteana W1 fraction had MIC of 252 ug/ml for M. ulcerans. In PBMCs viability analysis, lymphocytes treated with R. acuminatissima and E. milanjiana had the lowest cell viability. Betulinic acid, 1,2,3,6-tetra(3,4,5-trihydroxyphenyl) acetyl ester - B-D glucopyranose and cyclanoline exhibited good synergistic antimycobacterial activity with SIRE drugs at 18ug/ml for MDR-TB. In the heavy metal analysis, all the plants under study displayed the least level of toxic metal order of Cadmium<chromium<lead. In conclusion, this study is the first to report on isolation, characterisation and activities of novel compounds 1,2,3,6 - tetra(3,4,5 trihydroxyphenyl) acetyl ester - B-D- glucopyranose and Cyclanoline and E5 from medicinal plants understudy.
Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 μmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 μmol·L-1, respectively.
As part of our search for new secondary metabolites from Macaranga hurifolia Beille, a phytochemical investigation was carried out on the fruits that led to the isolation and characterization of two new prenylated flavonol derivatives named macafolias A (1) and B (2), along with five known compounds. Their chemical structures were established on the basis of extensive analysis of their 1–D and 2–D NMR (¹H, ¹³C, APT, COSY, HSQC and HMBC) in conjunction with mass spectroscopy and by comparison with data from the literature. The in vitro assay of the antibacterial potency of the crude extract, fractions and some pure compounds were evaluated against a wide range of bacteria strains.
Sophora flavescens Ait. has been utilized as an anticarcinogen, antibacterial and insecticide. Two new prenylflavonoids, Sophoflavonoid A (1) and Sophoflavonoid B (2), together with four known analogues were isolated from the root bark of S. flavescens. The structures of these compounds were elucidated by the interpretation of spectroscopic data and chemical evidence. Their absolute configurations were determined by ECD analysis. The inhibitory effects of compounds 1–6 against three lung carcinoma cells were determined using the MTT assay. The results revealed that compound 3 displayed strong cytotoxic effect against H460 cell line (IC50, 4.67 μM), while compounds 1, 4–6 exhibited significant inhibitory effects against three tumor cells. Therefore, this study suggests that the isopentenyl flavonoid-rich products of S. flavescens, including the new compounds, could be valuable candidates for the development of pharmaceuticals in the prevention and treatment for tumors.
Tuberculosis (TB) and human immunodeficiency virus (HIV) can place a major burden on healthcare systems and constitute the main challenges of diagnostic and therapeutic programs. Infection with HIV is the most common cause of Mycobacterium tuberculosis (Mtb), which can accelerate the risk of latent TB reactivation by 20‐fold. Similarly, TB is considered the most relevant factor predisposing individuals to HIV infection. Thus, both pathogens can augment one another in a synergetic manner, accelerating the failure of immunological functions and resulting in subsequent death in the absence of treatment. Synergistic approaches involving the treatment of HIV as a tool to combat TB and vice versa are thus required in regions with a high burden of HIV and TB infection. In this context, plant systems are considered a promising approach for combatting HIV and TB in a resource‐limited setting because plant‐made drugs can be produced efficiently and inexpensively in developing countries and could be shared by the available agricultural infrastructure without the expensive requirement needed for cold chain storage and transportation. Moreover, the use of natural products from medicinal plants can eliminate the concerns associated with antiretroviral therapy (ART) and anti‐TB therapy (ATT), including drug interactions, drug‐related toxicity and multidrug resistance. In this review, we highlight the potential of plant system as a promising approach for the production of relevant pharmaceuticals for HIV and TB treatment. However, in the cases of HIV and TB, none of the plant‐made pharmaceuticals have been approved for clinical use. Limitations in reaching these goals are discussed.
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Phytochemical reinvestigation on the whole plants of Derris laxiflora Benth. afforded two new diprenylated flavanones, derriflavanones B and C (1–2), together with thirty-two known compounds, including sixteen flavonoids (3–18), eleven aromatic compounds (19–29), and five chlorophylls (30–34). All known compounds were first isolated from this plant. The structures of these compounds were determined by analysis of the NMR spectroscopy, mass data, IR spectra, UV spectra, optical rotation and by comparison with literature data.
Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.
Four prenylated flavonoids compounds 1–4, named sinopodophyllines A–D, and a flavonoid glycoside (compound 13), sinopodophylliside A, together with 19 known compounds (compounds 5–12 and 14–24) were isolated from the fruits of Sinopodophyllum hexandrum. The structures of new compounds were elucidated by extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR. Compounds 1–6, 9–11, and 14–17 were tested for their cytotoxicity against human breast-cancer T47D, MCF-7 and MDA-MB-231 cells in vitro, and compounds 2, 5, 6, 10 and 11 showed significant cytotoxicity (IC50 values < 10 μmol·L⁻¹) against T47D cells.
Bioassay-guided phytochemical investigation of the EtOAc fraction (ST-EtOAc) from the roots of Sophora tonkinensis resulted in the isolation of a new compound 1-hydroxy-4-isoprenyl-maackiain (1), along with 12 known compounds (2-13). The structure of the new compound was established by 1D and 2D NMR, MS data and circular dichroism analysis. Polyprenylated flavonoids 6-9 and 11-13 increased GLUT-4 translocation by the range of 1.35-2.75 folds. Sophoranone (8) exerted the strongest activity with 2.75 folds GLUT-4 translocation enhancement at the concentration of 10 μM. This is the first report of the GLUT-4 translocation activity of the plant Sophora tonkinensis.
The word phytopharmaceutical deals with a complex mixture of compounds derived from the plant source that is used as a medicine or drug. Primitive human societies have been depending on plants and plant products for various remedies. Several plants in the different forms have been reported in traditional medicine and to find a rational for the treatment of various diseases than to isolated single compounds. Many of the single compounds isolated from the plant origin are effectively used in the medicine. The search of natural products in drug discovery has been greatly enhanced in the last few years. The impetus to use phytopharmaceutical agents for the treatment of disease, most of the plant based drugs are quite safe and have lesser adverse effects and are claimed that it works as synergistic effects.
Africa is a continent rich in biodiversity. It is endowed with vast resources of plants used by the people since time immemorial as medicines, flavors and fragrances. Of the 150,000 species of higher plants believed to occur in tropical countries 30,000 species divided into about 2,500 genera are found in Africa.
Phytochemical investigation of the ethanol extract of rhizomes of Iris tectorum resulted in the isolation and characterization of two new flavonoid glycosides, tectorigenin-7-O-β-d-fucopyranoside (1), 3,5,4′-trihydroxy-7,3′-dimethoxyflavanone-5-O-α-l-rhamnopyranoside (2), together with two known ones (3, 4). The rhamnose substituent at C-5 displayed uncommon connection in naturally occurring flavonoid glycosides. Their structures were elucidated on the basis of extensive spectroscopic analysis. All of the isolates were evaluated for their in vitro inhibitory activity against aldose reductase.
In this chapter, emphasis is given to the natural distribution of flavones and flavonols occurring in the free state. The relevant data are compiled in Tables 7.1–7. 7. In all, these tables list over 200 flavones and almost 300 flavonols with simple hydroxyl (or methoxyl) substitution patterns (Tables 7.1 and 7.2), thus stressing the earlier observation that flavonols predominate over flavones. Further, these tables contain more than 160 compounds with extra substituents (including compounds shown in Figs 7.3 and 7.4). Since the data for the previous edition (Wollenweber, 1982a) were compiled, some 40 flavones and 50 flavonols of the usual type have been reported as novel natural products (Tables 7.1 and 7.2), and some 50 novel flavonoids with extra substituents have also been added (Tables 7.3–7.7 and Figs 7.3 and 7.4).
A simple and efficient approach for synthesis flavonoids with 2,3-dihydroxy-3-methylbutyl moiety, by which seven natural prenylated flavonoids, brosimacutin A-B, brosimacutin D, brosimacutin E, brosimacutin H and brosimacutin M have been synthesized in racemic form. All structures of new compounds were confirmed by NMR and HRMS.
Three dihydroflavonol derivatives, macarecurvatin A (1), macarecurvatin B (2), and 6,8-diisoprenylaromadendrin (3) have been isolated from the leaves of Macaranga recurvata. The structures of these compounds were determined based on UV, IR, HRESIMS, 1D and 2D NMR data. All of compound isolated were evaluated for their inhibitory effect on scavenging DPPH radical and their growth inhibition on MCF7, and tamoxifen-resistant MCF7 (MCF7/TAMR) breast cancer cell showed high antioxidant and high cytotoxic activities.
The unique, high-affinity binding of cyanovirin-N (CV-N), a potent anti-human immunodeficiency virus (HIV) protein, to the HIV envelope glycoprotein gp120, was exploited to develop an HTS assay in an attempt to discover small-molecule mimetics of CV-N. A competition binding assay was developed using CV-N labeled with europium (Eu31). The labeling protocol did not significantly alter the gpl20 binding properties or the antiviral activity of CV-N. This report describes the assay development, validation, and results of screening a large library of aqueous and organic natural product extracts. The extracts were incubated with immobilized recombinant gpl20 in 96-well plates prior to the addition of Eu3+-labeled CV-N. Following a wash step, bound CV-N was measured by dissociation-enhanced time-resolved fluorometry of Eu3+. The assay proved to be robust, rapid, and reproducible, and was used to screen over 50,000 natural product extracts, and has resulted in the identification of several aqueous natural product extracts that inhibited CV-N-gp120 binding and also had anti-HIV activity.
The unique, high-affinity binding of cyanovirin-N (CV-N), a potent anti-human immunodeficiency virus (HIV) protein, to the HIV envelope glycoprotein gp120, was exploited to develop an HTS assay in an attempt to discover small-molecule mimetics of CV-N. A competition binding assay was developed using CV-N labeled with europium (Eu(3+)). The labeling protocol did not significantly alter the gp120 binding properties or the antiviral activity of CV-N. This report describes the assay development, validation, and results of screening a large library of aqueous and organic natural product extracts. The extracts were incubated with immobilized recombinant gp120 in 96-well plates prior to the addition of Eu(3+)-labeled CV-N. Following a wash step, bound CV-N was measured by dissociation-enhanced time-resolved fluorometry of Eu(3+). The assay proved to be robust, rapid, and reproducible, and was used to screen over 50,000 natural product extracts, and has resulted in the identification of several aqueous natural product extracts that inhibited CV-N-gp120 binding and also had anti-HIV activity.
Kaempferol (20) reacted with 2-methylbut-3-en-2-ol in the presence of boron trifluoride etherate to yield a mixture of the 6,8-di(3- methylbut-2-enyl) derivative (21), 3,5-dihydroxy-2-(4?-hydroxyphenyl)- 8,8-dimethyl-9,10-dihydro-4H,8H-benzo[1,2-b:3,4-b?]dipyran-4-one (19), and natural noranhydroicaritin(5). The orientation of the 3-methylbut- 2-enyl unit in the 8-position in the flavonol(5) has been unambiguously established by synthetic experiments. Complete acetylation of the flavonol (5) followed by reaction of the product (22) with one molar proportion of methyl iodide in the presence of dry potassium carbonate and acetone afforded 8-(3-methylbut-2-enyl)rhamnocitrin triacetate (23) which, on deacetylation, gave natural isoanhydroicaritin3 (4). 3- Methylbut-2-enylation of kaempferol 3,4?-dimethyl ether (7) was effected in two ways and the products [(8), (9) and (10)]were oxidatively cyclized with 2,3-dichloro-5,6-dicyano-p-benzoquinone to make available the corresponding monopyrano derivatives (26)-(29) to act as reference compounds for investigation of natural products. The 3-methoxyflavone (10) was also converted into di-O-methylicaritin (24) via the partial methyl ether (17a).
Isolation of four new isoflavones from a new collection of Millettia pachycarpa is reported. Proof of the structure of lupinifolol, previously isolated from M. pachycarpa, by synthesis of dehydrolupinifolol is described.
Flavanones of 2S configuration and 3-hydroxyflavanones of 2R,3R configuration, having equatorial 2-aryl substituents in the former or diequatorial 2,3-substituents in the latter, exhibit a positive Cotton effect due to the n → π* transition (∼ 330 nm) and a negative Cotton effect in the n α π* region (∼ 280–290 nm). Flavanone glycosides possessing chiral aglycones show Cotton effects quite similar to their optically active aglycones while flavanone glycosides having racemic aglycones show only weak Cotton effects at 250–350 nm. The π → π* Cotton effect is more suitable for determining aglycone chirality in flavanone glycosides. In addition to the two high wavelength bands, 2S-flavanones generally showed a positive Cotton effect at 245–270 nm and a negative Cotton effect at 225–240 nm. trans 2R,3R-3-Hydroxyflavanones gave two Cotton effects below 270 nm both of which were positive.
The CH2Cl2 extract of Monotes engleri Gilg. (Dipterocarpaceae) showed antifungal activity against the yeast Candida albicans in our bioautographic TLC assays. After a first fractionation of the crude extract, the bioactivity was located in one of the fractions. To perform an efficient targeted isolation of the active compounds, LC/UV/MS and LC/UV/NMR analyses of the crude extract and the active fraction were performed. LC/UV/, LC/MS, and LC/NMR data (1D and 2D) allowed the identification of 1 as (2S)-2,3-dihydro-5,7-dihydroxy–{3-hydroxy-4-[(3-methylbut-2-enyl) oxy]phenyl}-4H-1-benzopyran-4-one, a new prenylated flavanone, named monoteson A. Subsequent isolation of 1 has permitted the determination of its absolute configuration on the basis of CD measurements. Theree other prenylated flavanoes 2–4 were isolated from the same extract. Compound 3 was identified as 2- (3, 5-dihydroxyphenyl) -2,3-dihydro-5, 7-dihydroxy-6, 8-bis (3-methylbut-2-enyl)-4 H-1-benzopyran-4-one, another new natural product, named monotesone B. The structures of 2 and 4 were established as selinone and lonchocarpol A, respectively. The antifungal activity against Candida albicans was determined for all compounds.
Five novel flavanones have been isolated from the leaves of the Costa Rican treeLonchocarpus minimiflorus, and characterized on the basis of their spectral features. Three of these compounds contain an uncommon prenyl cyclization, new to flavanone chemistry.
The methanolic extract of the leaves of Macaranga vedeliana furnished a new flavonol, macarangin (6-[(E)-3″,8″-dimethyl-2″,7″-octadienyl]kaempferol).
We are implementing a series of complementary assays for initial follow-up confirmation and prioritization of new active anti-HIV compounds identified by the U.S. National Cancer Institute's large-scale in vitro primary anti-HIV screen. Two different kinds of cellular viability assays, in addition to specific assays for total cellular DNA content, supernatant reverse transcriptase activity, p24 core antigen production and the synthesis of infectious HIV virions are all performed from a single well of a 96-well microtiter plate containing human host cells infected with HIV. Antiviral activities of several known prototype HIV inhibitors including 3'-azido,3'-deoxythymidine, 2',3'-dideoxycytidine, dextran sulfate and phorbol myristate acetate were compared in these multiparameter assays as a means of validation. Procedures to automate the method optimally, as well as to maximize the safety of the technicians working with HIV and HIV-infected cells have been emphasized. The resulting semiautomated, highly reproducible battery of assays yields a maximum amount of antiviral and cytotoxicity information from a minimum amount of sample. This is especially crucial when analyzing new synthetic compounds and natural product extracts or fractions where the available amounts of sample may be very limited.
Of a variety of flavanoids, the flavans were generally more effective than flavones and flavanones in selective inhibition of HIV-1, HIV-2 or SIV infection. Studies of their effects on the binding of sCD4 and antibody to gp120 indicated that the effective compounds interact irreversibly with gp120 to inactive virus infectivity and block infection.
New cytotoxic isomalabaricane triterpenes have been isolated from a sponge Stelletta sp. (1-7); anti-HIV pterocarpans (8 and 9) and isoflavanoids (12-16 and 18) were elucidated from two tropical plants in the genus Erythrina; and anti-HIV enniatins (20 and 22-23) were characterized from fungi in the genera Fusarium and Alternaria. The enniatins were evaluated for in vivo anti-HIV activity in the hollow fiber assay.
From the leaves of Monotes engleri, five prenylated flavanones were isolated as constituents that displayed cytotoxic activity against several human cancer cell lines. There of these substances are novel, namely, 6-(1,1-dimethylallyl)naringenin, 6-(1,1-dimethylallyl)eriodictyol and 3'-O-methyl-6-(1,1-dimethylallyl)-eriodictyol, with the other two active substances being the known flavanones, 6,8-diprenyleriodictyol and hiravanone. Additionally, two novel, but non-cytotoxic, biogenetically related flavanones were isolated, 6-[(2RS)-hydroxy-3-methyl-3-butenyl]-8-prenyleriodictyol and 5,4'-dihydroxy-4",4"-dimethyl-5"-methyl-5"H-dihydrofurano[2",3": 6,7]flavanone. The structures of the new compounds were determined by spectral analysis 1D- and 2D-NMR experiments.
Many compounds of plant origin have been identified that inhibit different stages in the replication cycle of human immunodeficiency virus (HIV): 1) virus adsorption: chromone alkaloids (schumannificine), isoquinoline alkaloids (michellamines), sulphated polysaccharides and polyphenolics, flavonoids, coumarins (glycocoumarin, licopyranocoumarin) phenolics (caffeic acid derivatives, galloyl acid derivatives, catechinic acid derivatives), tannins and triterpenes (glycyrrhizin and analogues, soyasaponin and analogues); 2) virus-cell fusion: lectins (mannose- and N-acetylglucosamine-specific) and triterpenes (betulinic acid and analogues); 3) reverse transcription; alkaloids (benzophenanthridines, protoberberines, isoquinolines, quinolines), coumarins (calanolides and analogues), flavonoids, phloroglucinols, lactones (protolichesterinic acid), tannins, iridoids (fulvoplumierin) and triterpenes; 4) integration: coumarins (3-substituted-4-hydroxycoumarins), depsidones, O-caffeoyl derivatives, lignans (arctigenin and analogues) and phenolics (curcumin); 5) translation: single chain ribosome inactivating proteins (SCRIP's); 6) proteolytic cleavage (protease inhibition): saponins (ursolic and maslinic acids), xanthones (mangostin and analogues) and coumarins; 7) glycosylation: alkaloids including indolizidines (castanospermine and analogues), piperidines (1-deoxynojirimicin and analogues) and pyrrolizidines (australine and analogues); 8) assembly/release: naphthodianthrones (hypericin and pseudohypericin), photosensitisers (terthiophenes and furoisocoumarins) and phospholipids. The target of action of several anti-HIV substances including alkaloids (O-demethyl-buchenavianine, papaverine), polysaccharides (acemannan), lignans (intheriotherins, schisantherin), phenolics (gossypol, lignins, catechol dimers such as peltatols, naphthoquinones such as conocurvone) and saponins (celasdin B, Gleditsia and Gymnocladus saponins), has not been elucidated or does not fit in the proposed scheme. Only a very few of these plant-derived anti-HIV products have been used in a limited number of patients suffering from AIDS viz. glycyrrhizin, papaverine, trichosanthin, castanospermine, N-butyl-1-deoxynojirimicin and acemannan.
A new carbazole alkaloid, siamenol (1), and two known alkaloids, mahanimbine (2) and mahanimbilol (3), have been isolated from the organic extract of Murraya siamensis. The novel compound exhibited HIV-inhibitory activity.
A new coumarin, 5-(4-hydroxyphenethenyl)-4,7-dimethoxycoumarin (1) was isolated from the combined ethyl acetate extracts of the root bark, root wood and stem bark of Monotes engleri, and found to be cytotoxic against two cell lines in a human tumor panel. Its structure was determined on the basis of spectroscopic methods.
- E Garo
- J.-L Wolfender
- K Hostettmann
- W Hiller
- S Antus
- S Mavi
Garo, E.; Wolfender, J.-L.; Hostettmann, K.; Hiller, W.; Antus, S.;
Mavi, S. Helv. Chim. Acta 1998, 81, 754-763.
- V Cody
- E Middleton
- Jr
- J B Harborne
- R Alan
- Liss
(6) Cody, V., Middleton, E., Jr., Harborne, J. B., Eds. Plant Flavonoids
in Biology and Medicine; Alan R. Liss: New York, 1985; Vol. 213.
- A K Singhal
- R P Sharma
- K P Madhusudanan
- G Thyagarajan
- W Herz
- S Govindan
Singhal, A. K.; Sharma, R. P.; Madhusudanan, K. P.; Thyagarajan,
G.; Herz, W.; Govindan, S. V. Phytochemistry 1981, 20, 803-806.
- T Hatano
- T Yasuhara
- K Miyamoto
- T Okuda
Hatano, T.; Yasuhara, T.; Miyamoto, K.; Okuda, T. Chem. Pharm.
Bull. 1988, 36, 2286-2288.
- N Mahmood
- C Pizza
- R Aquino
- N Detommasi
- S Piacente
- S Colman
- A Burke
- A Hay
Mahmood, N.; Pizza, C.; Aquino, R.; DeTommasi, N.; Piacente, S.;
Colman, S.; Burke, A.; Hay, A. J. Antiviral Res. 1993, 22, 189-199.
- A C Jain
- R K Gupta
Jain, A. C.; Gupta, R. K. Aust. J. Chem. 1975, 28, 607-619.
- E Hnawia
- O Thoison
- F Guéritte-Voegelein
- D Bourret
- T Sévenet
Hnawia, E.; Thoison, O.; Guéritte-Voegelein, F.; Bourret, D.; Sévenet,
T. Phytochemistry 1990, 29, 2367-2368.