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Novel cytotoxic polyprenylated xanthonoids from Garcinia gaudichaudii (Guttiferae)

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Abstract

Cytotoxicity guided phytochemical analysis of the leaf extract of the Malaysian medicinal plant Garcinia gaudichaudii led to the isolation of 15 novel cytotoxic compounds, gaudichaudiones A - H (1,2,8 – 10 and 12), gaudichaudiic acids A - E (3 – 6), including the known morellic acid (7) and forbesione (11). All are mainly tetraprenylated xanthonoids but gaudichaudione H (12) is a novel bridgehead methoxylated triprenylated xanthonoid. The novel caged structures were determined by detailed NMR spectral analysis and the compounds were found to exhibit significant cytotoxicity against several cancer cell lines.

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... Investigation of the leaves of Garcinia wightii afforded two new caged xanthones, wightiic acid (1) and 16-O-methyl wightiic acid (2), along with eight known compounds including two caged xanthones; (−)-gaudichaudic acid E (3) and (−)-isogaudichaudic acid E (4), four triterpenoids; ursolic acid (5), lupeol (7), glutinol (8) and lupenone (9) and two steroids; stigmasterol (6) and stigmasteryl linoleate (10) [7][8][9][10][11][12][13]. ...
... UV absorption bands (λ max 291 and 353 nm) were similar to that of compounds 3 and 4 [8]. 1 H and 13 C NMR spectra of the compounds 1 and 2 showed similar signals to that of compounds 3 and 4, belonging to caged xanthones. A singlet of the hydrogen bonded phenolic hydroxyl group (1-OH), a doublet corresponding to the olefinic proton (H-8), a multiplet of a methine proton (H-7), an overlapped peak and a doublet of doublets of methylene group (H-25a and H-25b respectively), a doublet of methine group (H-26) and two methyl groups (H-28 and H-29) were assigned to the protons of the caged ring A [7,8]. ...
... In addition to the basic skeleton, 1 H NMR and HMQC spectra indicated the presence of three coupled systems. The [7]. The structure was confirmed through HMBC correlations from H-16 (δ H 5.12) to C-17 (δ C 76.9), H-17 (δ H 4.66) to C-16 (δ C 67.1), H-19 (δ H 1.59) to C-17 (δ C 76.9) and C-18. ...
Article
Two new caged xanthones, wightiic acid (1) 16-O-methyl wightiic acid (2), along with eight known compounds, gaudichaudic acid E (3), isogaudichaudic acid E (4), ursolic acid (5) stigmasterol (6), lupeol (7), glutinol (8), lupenone (9) and stigmasteryl linoleate (10) were isolated from Garcinia wightii T. Anderson. The structures of the compounds were elucidated by spectroscopic means, including 1D and 2D NMR, HR-ESIMS, and the absolute configuration of the new compounds 1 and 2 were determined by analysis of ECD data. Anti-proliferation activities of the four caged xanthones (1–4) were evaluated by MTT assay on MCF-7 and SKBR-3 human breast cancer cells and A-375 human melanoma cells by MTT assay. All the tested compounds exhibited dose dependent antiproliferative activity. Wightiic acid (1) showed remarkable activity with IC50 value of 4.7 μM and 5.2 μM respectively in A-375 and MCF-7 cells. The compound isogaudichaudic acid E (4) induced potent antiproliferation against SKBR-3 cells with an IC50 value of 6.1 μM.
... In 1998, Cao et al. [81] isolated a set of five caged carboxyxanthone derivatives from the leaf extract of Garcinia gaudichaudii, namely, gaudichaudiic acids A-E (71)(72)(73)(74)(75). Later, in 2000, other caged carboxyxanthone derivatives, gaudichaudiic acids F-I (76-79), were reported by Xu et al. [82]. In both studies, compounds 71-79 ( Figure 5) were tested for cytotoxicity against several cell lines, including P388/DOX and Messa [82], P388 [81,82], WEHI1640, MOLT4, HePG2, and LL/2 [81]. ...
... In 1998, Cao et al. [81] isolated a set of five caged carboxyxanthone derivatives from the leaf extract of Garcinia gaudichaudii, namely, gaudichaudiic acids A-E (71)(72)(73)(74)(75). Later, in 2000, other caged carboxyxanthone derivatives, gaudichaudiic acids F-I (76-79), were reported by Xu et al. [82]. In both studies, compounds 71-79 ( Figure 5) were tested for cytotoxicity against several cell lines, including P388/DOX and Messa [82], P388 [81,82], WEHI1640, MOLT4, HePG2, and LL/2 [81]. It was found that all compounds showed cytotoxic activity against P388 cell line. ...
... In 1998, Cao et al. [81] isolated a set of five caged carboxyxanthone derivatives from the leaf extract of Garcinia gaudichaudii, namely, gaudichaudiic acids A-E (71)(72)(73)(74)(75). Later, in 2000, other caged carboxyxanthone derivatives, gaudichaudiic acids F-I (76-79), were reported by Xu et al. [82]. In both studies, compounds 71-79 ( Figure 5) were tested for cytotoxicity against several cell lines, including P388/DOX and Messa [82], P388 [81,82], WEHI1640, MOLT4, HePG2, and LL/2 [81]. It was found that all compounds showed cytotoxic activity against P388 cell line. ...
Article
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Xanthones represent a structurally diverse group of compounds with a broad range of biological and pharmacological activities, depending on the nature and position of various substituents in the dibenzo-γ-pyrone scaffold. Among the large number of natural and synthetic xanthone derivatives, carboxyxanthones are very interesting bioactive compounds as well as important chemical substrates for molecular modifications to obtain new derivatives. A remarkable example is 5,6-dimethylxanthone-4-acetic acid (DMXAA), a simple carboxyxanthone derivative, originally developed as an anti-tumor agent and the first of its class to enter phase III clinical trials. From DMXAA new bioactive analogues and derivatives were also described. In this review, a literature survey covering the report on carboxyxanthone derivatives is presented, emphasizing their biological activities as well as their application as suitable building blocks to obtain new bioactive derivatives. The data assembled in this review intends to highlight the therapeutic potential of carboxyxanthone derivatives and guide the design for new bioactive xanthone derivatives.
... Garcinia species from the Guttiferae family have attracted a great deal of interest due to the chemical diversity and bioactivity of their secondary metabolites, which include xanthones, benzophenones, flavonoids, and depsidones [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Some of these compounds exhibited significant biological effects, such as antitumor, cytotoxic, anti-HIV, antibacterial, and antioxidant activities [16][17][18][19][20][21][22]. ...
... In the HMBC spectrum, the proton signal at δ H 7.25 (H-8) correlated with the carbonyl carbon signal at δ C 179.9 (C-9), which is characteristic for the carbonyl group of a xanthone skeleton. This signal (H-8) also correlated with the other carbonyl carbon signal at δ C 203.4 (C-6), which is typically found in caged-xanthone structures [4]. The correlations of the methine proton at δ H 2.80 (H-22) to the carbon signals at δ C 89.0 (C-4b), δ C 80.0 (C-7), δ C 33.4 (C-21), and δ C 84.2 (C-23), as well as of the methylene protons at δ H 1.82 (H-21a) and δ H 2.27 (H-21b) to the carbon signals at δ C 80.0 (C-7), δ C 138.6 (C-8), and δ C 84.2 (C-23) further confirmed the caged structure of compound 1. ...
... Four known xanthones, gaudichaudione H, 1,7-dihydroxy-3-methoxy-2-(3-methyl-2-butenyl)xanthone, 1,5-dihydroxy-3-methoxy-2-(3-methyl-2butenyl)xanthone and 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)xanthone, as well as lupeol were isolated and identified by comparison of their spectral data with those published in the literature [1,2,4]. The isolated compounds were assayed for cytotoxicity on MCF-7, NCI-H460 and DU-145 cell lines to establish their activity and potential selectivity, and the results are presented in Table 3. Gaudichaudione H and 1,5-dihydroxy-3-methoxy-2-(3-methyl-2-butenyl)xanthone exhibited the highest cytotoxic activity towards all three cell-lines with no selectivity, and with IC 50 values ranging from 6.6 μM to 8.9 μM. ...
Article
Full-text available
Two new xanthones, 7-hydroxydesoxymorellin (1) and isocaledonixanthone D (2), and four known ones, gaudichaudione H, 1,7-dihydroxy-3-methoxy-2-(3-methyl-2-butenyl)xanthone, 1,5-dihydroxy-3-methoxy-2-(3-methyl-2-butenyl)xanthone, and 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)xanthone, as well as lupeol were isolated from the leaves of Garcinia urophylla (Guttiferae). Their structures were determined using a combination of ID ('H NMR, C-13 NMR, DEPT) and 2D (COSY, gHSQC, gHMBC) NMR spectroscopic techniques. Among the isolates, 7-hydroxydesoxymorellin (1), gaudichaudione H, 1,5-dihydroxy-3-methoxy-2-(3-methyl-2-butenyl)xanthone, and 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)xanthone demonstrated cytotoxic activities against breast (MCF-7), prostate (DU-145), and lung (NCI-H460) human cancer cell lines.
... 3,7 ]decan-2-one scaffold with a common xanthone backbone. 5 This motif is further elaborated by substitutions on the aromatic residue and peripheral oxidations to produce a variety of structurally diverse caged Garcinia xanthones shown in Figure 1, including gambogic acid (GA, 1), 6,7 gambogellic acid (2), 8 desoxymorellin (3), 9 gaudichaudione A (4), 10 gaudichaudione G (5), 10 and isobractatin (6). 11 Among these, 1 is the most prominent and representative example. ...
... 3,7 ]decan-2-one scaffold with a common xanthone backbone. 5 This motif is further elaborated by substitutions on the aromatic residue and peripheral oxidations to produce a variety of structurally diverse caged Garcinia xanthones shown in Figure 1, including gambogic acid (GA, 1), 6,7 gambogellic acid (2), 8 desoxymorellin (3), 9 gaudichaudione A (4), 10 gaudichaudione G (5), 10 and isobractatin (6). 11 Among these, 1 is the most prominent and representative example. ...
Article
Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D7.4, aqueous solubility and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, 2 compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.
... The results showed that the compound 1-(4'-bromophenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propene-1-one or BHM had a cytotoxic effect on HeLa human cervical cancer cells. The IC50 value of BHM of 53 M indicates that this compound has the potential to be developed as an anti-cancer [21], while according to Cao [22], the anticancer activity of BHM is in the active category. When compared to its activity on breast cells (IC50= 45 M) [17], BHM is more potent in breast cancer. ...
Conference Paper
Chalcone and its derivatives are compounds known to have the potential activity of anticancer. We synthesized many para hydroxy chalcone derivates. One of these compounds was 1-(4’-bromophenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propene-1-on or BHM. This research aimed to investigate BHM as an anticancer in HeLa cervical cancer cells. The studies were cytotoxic tests and observation of apoptosis and Bcl-2 protein expression. The cytotoxicity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay. Cells apoptosis were determined using Annexin V Apoptosis Detection Kits followed by observed used a flow cytometer. The Bcl-2 protein expression was observed using immunocytochemistry methods. The results showed that BHM has cytotoxic activity and have potential as an anticancer with an IC50 value of 53 µM. BHM induced cell death of HeLa and suppressed the expression of Bcl-2 protein. This research needs to be studied further to investigate the mechanism pathway in inhibiting cancer cells. However, this study implies that 1-(4’-bromophenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propene-1-on can be a drug candidate for treat cervix cancer.
... The US National Cancer Institute has set a criterium of IC50 value above 20 µg/mL for the extract and fraction, and 4 µg/mL for the compound to be categorized as non-cytotoxic [26]. It is also reported that an extract or fraction with IC50 value of less than 5 µg/mL was classified as strongly toxic, 5-10 µg/mL toxic, 11-30 µg/mL mildly toxic, and more than 30 µg/mL non-cytotoxic [27]. Therefore, based on the criteria, the extract did not exhibit any cytotoxicity effects on the HepG2 cell line. ...
Article
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Atherosclerosis is the main cause of cardiovascular diseases which in turn, lead to the highest number of mortalities globally. This pathophysiological condition is developed due to a constant elevated level of plasma cholesterols. Statin is currently the widely used treatment in reducing the level of cholesterols, however, it may cause adverse side effects. Therefore, there is an urgent need to search for new alternative treatment. PCSK9 is an enzyme responsible in directing LDL-receptor (LDL-R)/LDL-cholesterols (LDL-C) complex to lysosomal degradation, preventing the receptor from recycling back to the surface of liver cells. Therefore, PCSK9 offers a potential target to search for small molecule inhibitors which inhibit the function of this enzyme. In this study, a marine invertebrate Acanthaster planci, was used to investigate its potential in inhibiting PCSK9 and lowering the levels of cholesterols. Cytotoxicity activity of A. planci on human liver HepG2 cells was carried out using the MTS assay. It was found that methanolic extract and fractions did not exhibit cytotoxicity effect on HepG2 cell line with IC50 values of more than 30 µg/mL. A compound deoxythymidine also did not exert any cytotoxicity activity with IC50 value of more than 4 µg/mL. Transient transfection and luciferase assay were conducted to determine the effects of A. planci on the transcriptional activity of PCSK9 promoter. Methanolic extract and Fraction 2 (EF2) produced the lowest reduction in PCSK9 promoter activity to 70 and 20% of control at 12.5 and 6.25 μg/mL, respectively. In addition, deoxythymidine also decreased PCSK9 promoter activity to the lowest level of 60% control at 3.13 μM. An in vivo study using Sprague Dawley rats demonstrated that 50 and 100 mg/kg of A. planci methanolic extract reduced the total cholesterols and LDL-C levels to almost similar levels of untreated controls. The level of serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) showed that the administration of the extract did not produce any toxicity effect and cause any damage to rat liver. The results strongly indicate that A. planci produced a significant inhibitory activity on PCSK9 gene expression in HepG2 cells which may be responsible for inducing the uptake of cholesterols by liver, thus, reducing the circulating levels of total cholesterols and LDL-C. Interestingly, A. planci also did show any adverse hepato-cytotoxicity and toxic effects on liver. Thus, this study strongly suggests that A. planci has a vast potential to be further developed as a new class of therapeutic agent in lowering the blood cholesterols and reducing the progression of atherosclerosis.
... The samples with IC 50 value more than 30 µg/mL were considered as having noncytotoxic properties, meaning that the samples can be used as antidiabetic, anti-cholesterol, and anti-inflammatory agents (Andriani et al., 2011). Cao et al. (1998) reported that a sample with IC 50 value less than 5 µg/mL is strongly toxic, 5-10 µg/mL toxic, 11-30 µg/mL mildly toxic and more than 30 µg/mL non-cytotoxic. The results revealed that nanoparticles of chitosan-P.tectorius ...
Article
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Pandanus tectorius fruit, a natural product rich in tangeretin and ethyl caffeate, has been reported to have potential as anti-hypercholesterolemia agent via Scavenger Receptor Class B type 1 (SR-B1) pathway. However, due to its semi-polar properties, P. tectorius extract exhibits poor solubility when used as a medical remedy. The extract’s solubility can potentially be improved through a synthesis of nanoparticles of chitosan-P. tectorius fruit extract. This can also increase the extract’s SR-B1 gene expression activity. To date, no studies of nanoparticles of chitosan-P. tectorius fruit extract and its pathway via SR-B1 have been published anywhere. In this study, cytotoxicity properties against HepG2 were explored by MTT. Then luciferase assay was used to detect their effectiveness in increasing SR-B1 activity. An in vivo study using Sprague dawley was carried out to observe the extract nanoparticles’ effectiveness in reducing the cholesterol levels and the toxicity property in rat’s liver. As the results showed, the extract nanoparticles had no cytotoxic activity against HepG2 cells and exhibited higher SR-B1 gene expression activity than the non-nanoparticle form. As the in vivo study proved, nanoparticle treatment can reduce the levels of TC (197%), LDL (360%), and TG (109 %), as well as increase the level of HDL cholesterol by 150%, in comparison to those for the untreated high-cholesterol diet group. From the toxicity study, it was found that there was non-toxicity in the liver. It can be concluded that nanoparticles of chitosan-P. tectorius fruit extract successfully increased P. tectorius fruit extract’s effectiveness in reducing hypercholesterolemia via SR-B1 pathway. Hence, it can be suggested that nanoparticles of chitosan-P. tectorius fruit extract is safe and suitable as an alternative treatment for controlling hypercholesterolemia via SR-B1 pathway.
... Compound 1, 3, and 4 had no effect at this concentration. IC 50 value showed no potential activity of the tested compounds due to the low value of IC 50 (IC 50 <30 µg/mL) 27 . ...
... Aktivitas antikanker sebesar 30,497 ppm dikategorikan ke dalam aktivitas sedang. 18 Bila dibandingkan dengan IC 50 , ekstrak etanol spon H. erecta sebelum diisolasi sebesar 26,35 ppm menunjukkan terjadi penurunan aktivitas antikanker terhadap sel HeLa setelah dimurnikan. 15 Hal ini membuktikan fenomena bahwa senyawa-senyawa yang mempunyai aktivitas biologis yang berasal dari bahan hayati umumnya bersifat sinergis. ...
Article
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Isolation, anticancer activity test, and identification of the toxic isolate from ethanol extract of the sponge Hyrtios erecta taken from Pari Island beach (Jakarta) has conducted. Extraction of the sponges was carried out by 70% ethanol at room temperature. Partition and purification of the compounds were done by column chromatography with the stationary phase of silica gel and the mobile phase of n-hexane-chloroform (2:8). Toxicity screening test was done based on BhrineShrimp Lethality Test (BSLT). In vitro anticancer activity test of the isolate was carried out using HeLa cell line. Identification of the compounds was performed by Gas chromatography-mass spectroscopy (GC-MS). Based on theresults, it was found that the toxic isolate of H. erecta sponges has anticancer activity with IC50 of 30,497 ppm. Four compounds was detected from the anticancer isolate i.e: 4-nonylphenol; dibutyl phthalate; hexanedioic acid bis(2-ethylhexyl) ester; and cholesterol. ABSTRAKTelah dilakukan isolasi, uji aktivitas antikanker, dan identifikasi isolat toksik yang berasal dari ekstrak etanol spons Hyrtios erecta yang diambil dari perairan Pulau Pari (Jakarta). Ekstraksi dilakukan dengan cara maserasi menggunakan etanol 70% pada temperatur kamar. Pemisahan dan pemurnian komponen menggunakan kromatografi kolom dengan fase diam silikagel dan fase gerak n-heksana-kloroform (2:8). Skrining toksisitas dilakukan dengan metode Bhrine Shrimp Lethality Test (BSLT). Uji antikanker secara in vitro isolat toksik tersebut menggunakan sel HeLa. Senyawanya diidentifikasi menggunakan Gas chromatography-mass spectroscopy (GC-MS). Berdasarkan hasil penelitian ini diperoleh bahwa isolat toksik spons H. erecta bersifat antikanker dengan IC50 sebesar 30,497 ppm. Pada isolat antikankertersebut terdeteksi empat senyawa, yaitu 4-nonylphenol; dibutil phtalat; ester heksadioat bis(2-etilheksil); dan kolesterol.
... One method used to conduct pre screening of the active anticancer compound is a cytotoxicity assay against the larvae of Artemia salina Leach or Brine Shrimp Lethality Test (BSLT) [19], [20]. The high toxicity of the test compound is highly correlated with the activity of anticancer compounds [14], [15]. ...
Article
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This research aims to isolate and phytochemically test of the toxic isolate from ethanol extract of the sponge Hyrtios erecta taken from the waters of Pari Island beach, Thousand Islands (Jakarta). Extraction of the sponges was carried out by 70% ethanol at room temperature. Partition and purification of the compounds were done by column chromatography with the stationary phase of silica gel and the mobile phase of n-hexane-chloroform (2:8). Toxicity screening test was done based on Bhrine Shrimp Lethality Test (BSLT). The compounds of the active isolate were performed by phytochemical test. Based on the results, it was found that the toxic isolate of Hyrtios erecta sponges has anticancer activity with IC50 of 30,497 ppm. The anticancer isolate contained alkaloid, steroid, and polyphenol compounds
... A substantial number of studies on the antitumor activities of Garcinia species have been reported and their activities were often attributed to the presence of xanthones , triterpenes, depsidones and benzophenones (Cao et al., 1998; Xu et al., 1998 Xu et al., , 2000 Mackeen et al., 2000; Thoison et al., 2000; Matsumoto et al., 2003b). The chemopreventive effects of xanthones and benzophenones from G. assigu and G. fusca were also reported (Ito et al., 2003aIto et al., , 2003b ). ...
Article
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The methanol extracts of 32 plant parts of 19 species of the genus Garcinia (Guttiferae) were collected from rainforests of the Malaysian Peninsula and the island of Sumatra, Indonesia, for evaluation of their in vitro cytotoxic and nitric oxide inhibitory activities. An end-point MTT cell viability assay was used to determine the 50% inhibitory concentration (IC50) of the extracts in three human tumor cell lines representing tumors of the breast (MCF-7), lung (NCI-H460) and prostate (DU-145). Griess assay was performed to assess the nitric oxide (NO) inhibitory activity. Of the 32 extracts, 27 showed cytotoxic activity in at least one of the three tumor cell lines used in this study. Four extracts, Garcinia opaca King (fruit), Garcinia maingayi Hook.f. (stem), Garcinia penangiana Pierre (leaf) and Garcinia urophylla Scortech.ex King (leaf) extracts showed the most potent and selective cytotoxic activity against MCF-7 cells (IC50 3-8 μg/mL). The extracts from Garcinia cowa Roxb. (stem), Garcinia bancana Miq. (stem) and Garcinia malaccensis Hook.f. (leaf) showed moderate activity and selectivity towards non-small lung tumor cells. The extracts from Garcinia bancana (stem), Garcinia malaccensis (stem), Garcinia prainiana King (leaf), Garcinia rostrata Hassk.ex Hook.f. (stem and leaf), Garcinia cowa (stem) and Garcinia nervosa Miq. (leaf) exhibited inhibition against NO production without affecting the viability of LPS and IFN-γ-induced RAW 264.7 macrophage cells. Among these, the most promising extracts were G. bancana (stem) and G. malaccensis (stem), as they showed the highest selectivity indices (> 50) for NO inhibition. In conclusion, these data provide evidence that some of the Garcinia species could potentially contain potent and selective cytotoxic and anti-inflammatory agents.
... This is exemplified by the structure of forbesione (8), a natural product isolated from Garcinia forbesii [15] and Garcinia hanburyi. [16] For example, prenylation at the C5 center of forbesione (gambogic acid numbering) gives access to the gaudichaudione scaffold, [17] represented by deoxygaudichaudione (10). [18] Oxidation at the C30 center could then lead to gaudichaudione A (11). [17a] Alternatively, prenylation of 8 at C5, followed by cyclization with the pendant phenol gives access to the morellin scaffold, [19] represented by desoxymorellin (5). ...
Article
Natural products have been a great source of many small molecule drugs for various diseases. In spite of recent advances in biochemical engineering and fermentation technologies that allow us to explore microorganisms and the marine environment as alternative sources of drugs, more than 70 % of the current small molecule therapeutics derive their structures from plants used in traditional medicine. Natural-product-based drug discovery relies heavily on advances made in the sciences of biology and chemistry. Whereas biology aims to investigate the mode of action of a natural product, chemistry aims to overcome challenges related to its supply, bioactivity, and target selectivity. This review summarizes the explorations of the caged Garcinia xanthones, a family of plant metabolites that possess a unique chemical structure, potent bioactivities, and a promising pharmacology for drug design and development.
... Most of the caged xanthones from G. scortechinii, namely scortechinones A-T (41-60, Fig. 2), are bridgehead-methoxylated, tetraprenylated and have a C-7 bridgehead methoxyl group and a 2,2,3-trimethyldihydrofuran ring between C-3 and C-4 [72][73][74][75]. 26 xanthones ( Fig. 3), gaudichaudiones A-J (61-70), gaudichaudiic acids A-I (71-79), and 7-isoprenylmorellic acid (80), were found in the leaf and bark extract of G. gaudichaudii [10,[76][77][78][79]. Among them, gaudichaudiic acids G-I, contain an unusual toluene-fused dimethylpyran ring. ...
Article
Caged xanthones, characterized by a unique 4-oxa-tricyclo[4.3.1.0(3,7)]dec-2-one scaffold, are a special class of bioactive components mainly derived from the Garcinia genus (Guttiferae family). Around 100 compounds from this family have been reported to date and most of them have potent antitumor activity, with gambogic acid being the best representative. During the past decades, inspired by the unusual caged skeleton and remarkable bioactivity, scientists from various fields have shown increasing interest on these promising natural products. In this review, the plant resources, structural characteristics, total synthesis, biological activity and mechanisms of action, structure activity relationship, and anticancer drug development of these caged xanthones are described.
... In the course of a search for anticancer agents from natural sources, the ethyl acetate extract of the leaves of Garcinia bracteata (Clusiaceae), collected in Hoa Binh Province of Vietnam, was found to exhibit strong cytotoxicity against the KB cell line. Bioas-say guided fractionation of this extract afforded six new prenylated xanthones: bractatin (140), 1-O-methylbractatin (141), isobractatin (142), 1-O-methylisobractatin (143), 1-O-methyl-8-methoxy-8,8a- dihydrobractatin (144), and 1-O-methylneobractatin (145) (Fig. (15)) [139]140141142. It seems that this genus could exist in two sections, the first one including species with classical xanthones, and the other one including species with molecules having the rearranged skeleton, the socalled caged xanthanoids, as in G. bracteata, G. morella, G. forbesii , G. gaudichaudii and G. hanburyi. For example, neoisobractatin A (146) and neoisobractatin B (147) (Fig. (15)), also isolated from the leaves of Garcinia bracteata, belong to the later section and were found to possess strong cytotoxicity against KB cell lines (IC 50 : 0.14 and 0.16 M respectively) [143]. ...
Article
Xanthones have been isolated from several natural sources, mainly belonging in Guttiferae and Gentianaceae families as secondary plant metabolites and many of them are endowed with diverse pharmacological properties. We have focused in the study of cytotoxic fused xanthone derivatives, having in mind that some furano- and pyranoxanthone natural products are particularly interesting, in terms of cytotoxic potency and novelty in their mechanism of action and could serve as lead compounds for the development of clinically effective anticancer agents. In this review, a general classification has been attempted based on the type of ring fusion, in such a way that natural compounds as well as synthetic derivatives are discussed. The furanoxanthone psorospermin is a highly promising isolated xanthone derivative exhibiting significant cytotoxicity through a novel mechanism of action, being an irreversible topoisomerase II poison and it was selected for further development as an antineoplastic agent. An important number of pyranoxanthones have been synthesized using as lead compound the acridone alkaloid acronycine. Adducts on the double bond of these compounds provided cytotoxic derivatives possessing cell-cycle selectivity. The synthesis of pyranoxanthones bearing aminosubstituted side-chains resulted in compounds that exhibit markedly improved cytotoxicity towards leukemic and solid tumor cell lines. Azabioisosters of the aminoderivatives exhibit solid tumor selectivity whereas additional pyrazole or/and benzene ring fusion has been incorporated into the xanthone skeleton and resulted in compounds with promising activity, which retain full antiproliferative activity against P-glycoprotein-overexpressing cells. Gambogic acid, a highly effective anticancer drug candidate with low toxicity to normal tissue, together with structurally related representative analogues are also mentioned.
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The average yield of G. gaudichaudii essential oil was 0.06%. Forty-two identified components in G. gaudichaudii essential oil presented 92.5% of the total compounds in the essential oil. The essential oil was characterized by sesquiterpene hydrocarbons (70.3%), followed by oxygenated sesquiterpenes (19.6%). The dominant compounds were identified as allo-aromadendrene (20.4%), β-caryophyllene (15.8%), δ-cadinene (10.6%), germacrene D (7.1%), α-copaene (5.4%), and caryophyllene oxide (5.2%).
Article
Background Xanthones, natural or synthetic, due to their wide range of biological activities, have become an interesting subject of investigation for many researchers. Xanthonic scaffold has proven to have a vital role in anticancer drug development since many of its derivatives have shown anticancer activities on various cell lines. In addition, targeting epigenetic markers in cancer has yielded promising results. There have also been reports on the impact of xanthone and related polyphenolic compounds on epigenetics markers in cancer prevention and therapy. Objective The objective of this review is to comprehensively highlight the main natural and non-natural sources of xanthones having potential anti-cancer effects along with their key structural elements, structure-activity relationships (SARs), mechanisms of action, and epigenetic profile of xanthone-based anti-cancer compounds. The challenges and future directions of xanthone-based therapies are also discussed briefly. Method The methods involved in the preparation of the present review included the collection of all recent information up to November 2021 from various scientific databases, indexed periodicals, and search engines such as Medline Scopus, Google Scholar, PubMed, PubMed Central, Web of Science, and Science Direct. Results Exploration of the diversity of the xanthone scaffold led to the identification of several derivatives having prominent anti-cancer activity. Their unique structural diversity and synthetic modifications showed the ongoing endeavour of enriching the chemical diversity of the xanthone molecular framework to discover pharmacologically interesting compounds. However, studies regarding their modes of action, pharmacokinetic properties, clinical data, epigenetics, and safety are limited. Conclusion Elucidation of the exact biological mechanisms and the associated targets of xanthones will yield better opportunities for these compounds to be developed as potential anticancer drugs. Further clinical studies with conclusive results are required to implement xanthones as treatment modalities in cancer.
Article
Nine compounds including a new one, garcichaudiic acid (1), were isolated from the bark of G. gaudichaudii and their structures were characterized mainly by 1 D and 2 D NMR experiments. The antioxidant capacity of the isolated compounds was determined using DPPH radical scavenging assay and the anti-hyperglycemic activity was assessed by measuring the inhibitory effect against α-glucosidase. Among them, compound 4 showed higher antioxidant activity than the positive control, ascorbic acid, while both compounds 1 and 7 exhibited more significant α-glucosidase inhibitory activity than the reference drug acarbose. Molecular docking analysis of the bioactive compounds was also performed to examine the binding modes and key interactions with the catalytic site.
Article
Gaudichaudione H (GH), a caged polyprenylated xanthone from Garcinia plants, showed anti-cancer and anti-inflammatory effects in vitro. However, the in vivo toxicity of this compound has never been reported. The present study was aimed to address the toxic effects of Gaudichaudione H using zebrafish embryos and larvae as an in vivo test model. The zebrafish embryos were treated with GH having different concentrations (0, 0.28, 0.38 and 0.57 μg/mL). The results revealed that GH induces significant embryonic mortality, decreased heartbeat, cardiotoxicity, cardiovascular defects, increased apoptosis and decreased hemoglobinization in zebrafish embryos and larvae. According to transcriptome analysis, 1841 genes were significantly differentially expressed (1185 down-regulated and 656 up-regulated) after GH treatment. The main functions of these genes were related to iron metabolism pathways. The toxicity of GH on zebrafish embryonic development and cardiovascular may due to large amounts of downregulated genes involved in metabolic pathways and DEGs related to ‘Iron ion binding’ and ‘Heme binding’ functions.
Article
Caged-polyprenylated xanthonoids represent a rare class of natural products. This type of compounds is mainly isolated from Genus Garcinia. Phytochemical studies on the leaves and twigs of Garcinia oligantha led to the isolation of four new caged-polyprenylated xanthonoids, oliganthone CF (1–4), and two new simple xanthones (5–6), oliganthaxanthone D and oliganthaxanthone E. Eight known other polyprenylated xanthones (7–14) including five caged-polyprenylated xanthonoids (7–11) were also isolated. Their structures were elucidated based on the analyses of extensive spectroscopic data. All the isolated compounds except for 5, 6 and 14 showed cell viability reducing effect against human lung cancer A549 cells. Compounds 1–3 were proved to be potential apoptosis inducing agents.
Article
Main observation and conclusion Nineteen unprecedented 7-methoxylated caged xanthones (1-19) were isolated from the twigs of Garcinia oligantha under the guidance of NMR spectroscopy. Their structures and absolute configurations were demonstrated by extensive spectroscopic data, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and the modified Mosher's method. Compound 1 is a rare scalemic 7-methoxylated neo-caged xanthone which was resolved using HPLC with CD detection on a chiral-phase AD column, and compounds 2-3 are rare 7-methoxylated caged xanthones with the hydrogenated Δ8(8a) double bond. Fourteen compounds exhibited promising inhibitory activities against four human cancer cell lines with IC50 values ranging from 1.9 to 14.3 μmol/L. A cell apoptosis analysis using flow cytometry showed that the compound 11 could induce apoptosis in a dose dependent manner. Moreover, PARP, caspase-9, and Bcl-2 western blotting suggested that compound 11-induced apoptosis maybe involved in caspase-dependent pathway. This article is protected by copyright. All rights reserved.
Chapter
Plants have been utilized for health and medicinal benefits for hundreds of years due to their multiple beneficial attributes such as anticancer, antitumor, antioxidant, antimicrobial, antibacterial, anti-ulcer, anti-arthritic, etc. It has been estimated that there are altogether 250,000 species of higher plants on Earth and among them 35,000–70,000 species are being used to treat various diseases due to the presence of secondary metabolites (alkaloids, flavonoids, steroids, glycosides, saponins, etc.). Cancer is a worldwide leading cause of morbidity and mortality. To cure this at right time, herbal drugs are more beneficial than synthetic drugs, because the synthetic medicines can cause heavy damage to normal cells while destroying the tumor cells. The present work consists of a review of 149 plant families harboring 667 species reported to possess anticancer property. Moreover, other biological properties of the bioactive compounds are also covered. This work is based on reliable data collected from multifarious databases such as CAB abstract, MEDLINE, EMBASE, J GATE, ERIC, Proquest, INMEDPLAN, NATTS, The Plant List, JSTOR, Google Scholar, Springer, Elsevier, and websites such as www.sciencedirect.com, www.jstor.org, www.eflora.org, and www.pfaf.org. The complete data regarding plant names, synonyms, common names, botanical description, medicinal properties, and bioactive compounds present in the plant parts is compiled. In near future, these bioactive compounds can be deployed singly or in combination with routine chemotherapy and radiotherapy to treat various types of cancers, after proper standardization, dose optimization, and stringent clinical trials.
Chapter
The Garcinia genus of plants has yielded an intriguing family of caged xanthone-derived natural products that have a documented value in traditional Eastern medicine. Collectively referred to as caged Garcinia xanthones (CGXs), these compounds are defined by an unusual motif in which the C-ring of an allylated xanthone has been converted into a tricyclic cage. This motif is further decorated via A-ring substitutions and peripheral oxidations to produce a variety of related subfamilies. Gambogic acid, the archetype of this family, has shown efficacy in several human tumor xenograft models and has entered clinical trials in China for the treatment of cancer. Its promising therapeutic potential has fueled the evolution of synthetic strategies, aiming to synthesize various natural products of this family and optimize its bioactive scaffold. This review will present the general chemical concepts that have been explored toward the synthesis of CGX natural products and will discuss how they have been applied for the study of the CGX pharmacophore.
Article
With bioassay- and chemistry-guided fractionation, seven new caged prenylxanthones including two scalemic mixtures, epiisobractatin (1), 13-hydroxyisobractatin (2), 13-hydroxyepiisobractatin (3), 8-methoxy-8,8a-dihydrobractatin (4), 8-ethoxy-8,8a-dihydrobractatin (5), garcibracteatone (6), and 8-methoxy-8,8a-dihydroneobractiatin (7), and the eight known compounds 8–15 were isolated from the leaves of Garcinia bracteata. The structures were unambiguously elucidated through analysis of spectroscopic data. The 2D structures and relative configurations of 1 and 5 were confirmed by X-ray crystallographic analysis. The separation of the enantiomers of 1–5 was accomplished by chiral-phase HPLC. The absolute configurations of the enantiomers of 1 and 5 were assigned by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The absolute configurations of the related compounds were determined via comparisons of their ECD data with those of the enantiomers of 1 and 5, respectively. Notably, compound 7, with a neo caged skeleton, is the first representative of a novel type of caged xanthone lacking a Δ8(8a) double bond. The isolated compounds exhibited significant cell growth inhibitory activities in vitro against human leukemic HL-60 and K562 cell lines, with GI50 values ranging from 0.2 to 8.8 μM. A preliminary structure–activity relationship is discussed.
Article
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Bioactivity of a compound is closely related to the molecular structure of the compound concerned, its strength being the quantitative relation of the strength of the activity of the group it possesses. The combining of moieties of the active compounds will produce more active compounds. Most phenolic compounds as well as compounds containing moiety phenethyl groups have potential activity as anticancer. Combining phenolic groups and phenethyl groups in a compound will result in compounds having strong anticancer bioactivity. This study aims to combine the feruloyl and phenethyl groups to form esters and amides by synthesize of phenethyl trans-3-(4-hydroxy-3-methoxyphenyl)acrylate (5) and trans-3-(4- hydroxy-3-methoxyphenyl)-N-phenethylacrylamide (6) from ferulic acid with phenethyl alcohol and phenethylamine, and to study their bioactivity as anticancer. The synthesis of both compounds was conducted via indirect reaction, including acetylation, chlorination, esterfication/amidation, and deacetylation. Structures of products were characterized by FTIR and NMR data, and their bioactivity assay of the compounds against P388 Leukemia Murine Cells was conducted by an MTT method. Results showed that the compound 5 was obtained as a yellow gel with the IC50 of 10.79 μg/mL (36.21 μΜ), and the compound 6 was a yellowish solid with a melting point of 118-120°C and the IC50 of 29.14 μg/mL (97.79 μΜ). These compounds were more active than the analog compounds.
Article
Seven new caged xanthones, doitunggarcinones E–K (1–7), all as scalemic mixtures and 10 known compounds (8–17), were isolated from the stem bark extract of Garcinia propinqua. The structures were elucidated on the basis of spectroscopic methods. The separation of the enantiomers of 1–6 was achieved by semipreparative chiral HPLC. The absolute configuration of compound (+)-1 was determined by single-crystal X-ray crystallographic analysis using Cu Kα radiation. The absolute configurations of the other related compounds were determined from comparisons of their ECD spectra with that of compound (+)-1. Compounds (−)-6 and 7 showed cytotoxicity against a colon cancer cell line with IC50 values of 14.23 and 23.95 μM, respectively.
Article
Four new dihydroxanthone derivatives (1-4), four new tetrahydroxanthone derivatives (5-8), two new xanthone derivatives (9 and 10), and two known caged tetrahydroxanthones were isolated from extracts of the leaves of Garcinia oligantha by bioassay-guided fractionation. These structures of the new compounds were elucidated by NMR and MS spectroscopic data analysis, and the absolute configurations of compounds 1 and 5-7 were determined by electronic circular dichroism and/or single-crystal X-ray diffraction analysis. Compounds 6-9 were shown to be unusual xanthone derivatives with an isopropyl group, which was confirmed by the X-ray crystallographic structure of compound 8. The inhibitory activities of these isolates against four human tumor cell lines (A549, HepG2, HT-29, and PC-3) were assayed, and compounds 1, 2, 5, 11, and 12 showed inhibitory effects on tumor cell growth, with IC50 values ranging from 2.1 to 8.6 μM.
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Garcinia forbesii is native to Malaysia and Indonesia (Sumatra, Kalimantan).
Article
Cancer is the second disease cause of mortality in USA, after cardiovascular diseases. Nowadays, the current research tend to develop anticancer agents from plants. One of the plants that can be used for anticancer therapy is the “ekor naga” leaves (Rhaphidophora pinnata (Lf) Schott), which is empirically used by some communities as breast cancer treatment.
Article
Cancer is second leading cause of death. World Health Organization estimates that 80% of the world's population still rely mainly on traditional medicines for their basic health care. During the last decades of the 20th century, medical researchers have developed new methods for cancer treatment by combining surgery with chemotherapy, radiations and various phytochemicals obtained from different plant species. It is important to note that chemotherapy not only kills the cancer cells but it has some side effects on normal cells too. Medicines obtained from plants have less or no side-effects. Present investigation is mainly concerned with the documentation of anti-cancer plant species around the globe. This database includes 576 plants describing their name, plant part used, active principle, families and various cell lines used in different studies. These plants are used directly or their extracts made in different solvents or only active components are isolated from the plant and used against cancer. Different plant parts like seeds, roots, fruit, flower, bud, stem, leaves and sometimes the whole plant have been used in cancer treatment.
Article
Two rare new natural products, the neocaged-xanthone pruniflorone T (1) and the rearranged caged-xanthone pruniflorone U (3), and the known caged-xanthone cochinchinone C (2) were isolated from the roots of Cratoxylum formosum ssp. pruniflorum. The unique structures of 1-3 were determined by analysis of NMR and X-ray diffraction data. The X-ray data of 1-3 revealed that they all exist with both enantiomers in their crystal packing. Separation of 1-3 by chiral HPLC led to the isolation of three pairs of enantiomers, (-)-1/(+)-1, (-)-2/(+)-2, and (-)-3/(+)-3, and their absolute configurations were determined by analysis of single-crystal X-ray diffraction and ECD spectroscopic data. A 1:1 mixture of 1 and 3 showed potent in vitro cytotoxicity against an MCF-7 human breast cancer cell line with an IC50 value of 0.11 μg/mL.
Article
Two novel caged ent-kauranoids, neolaxiflorins D (1) and E (2), along with three other new ent-kauranoids, neolaxiflorins F–H (3–5), and a known one, eriocalyxin B (6), were obtained from Isodon eriocalyx var. laxiflora. Neolaxiflorin D (1) is the first 15,16-seco-16,17-dinor-ent-kaurane diterpenoid, and neolaxiflorin E (2) is the first 15,16-seco-17-homo-ent-kauranoid. The absolute configurations of ent-kauranoids 1 and 2 were determined by single-crystal X-ray diffraction analyses. Structural analysis of intermediate compounds 3–5 indicated that eriocalyxin B (6) is a biogenetic precursor of caged ent-kauranoids 1 and 2 as illustrated. The cytotoxic activity of the new compounds was evaluated by an MTT assay.
Article
Lateriflorone (1), a cytotoxic natural product with an unprecedented spiroxalactone skeleton isolated from Garcinia lateriflora, has been characterized by NMR and X-ray crystallography studies as 6,21-bis(3-methylbut-2-enyl)-19-hydroxy-2,2,23,23-tetramethyl-13,15,22-trioxaspiro[6,7-dihydro-2H-chromene-7,4′-tetracyclo[7.4.1.02,7.02,11] tetradecane]-17-ene-5,8,16,20-tetraone.
Article
A further demonstration of the value of “biomimetically” inspired synthetic strategies toward natural products is provided by the title reactions that were developed for the construction of 4-oxatricyclo[4.3.1.0]decan-2-one systems from prochiral aromatic precursors. This biomimetic cascade was applied to the synthesis of 1-O-methylforbesione (2) from the prenylated xanthone 1 in one pot.
Article
The structures of novel gaudichaudiic acids F−I (1−4), isolated from the bark of Indonesian Garcinia gaudichaudii, have been elucidated by detailed spectral analysis. Gaudichaudiic acid I (4) is probably derived from 1 as a result of allylic oxidation at C-24 and C-21, followed by aromatization.
Article
During study on the remarkable cascade reaction for synthesis of compound 1, the neo-caged scaffold 2 with a heterocyclic bicyclo[2.2.2]octenone moiety and two new allyl substituted xanthones 3, 4 were obtained besides the known caged scaffold 1. The probable reaction processes were also elucidated in this paper.
Article
Three new xanthones, mangostenol (1), mangostenone A (2), and mangostenone B (3), were isolated from the green fruit hulls of Garcinia mangostana, along with the known xanthones, trapezifolixanthone, tovophyllin B (4), alpha- and beta-mangostins, gareinone B, mangostinone, mangostanol, and the flavonoid epicatechin. The structures of the new xanthones were elucidated by analysis of their spectroscopic data.
Article
Gaudispirolactone (1), a novel degraded and rearranged tetraprenylated xanthone isolated from the bark of Garcinia gaudichaudii, has the unique hexacyclic dioxospirotrione structure.
Article
Bioassay-guided fractionation allowed the isolation of two minor, caged cytotoxic tetraprenylated xanthonoids, gaudichaudiones I and J (1 and 2), from the leaf extract of Garcinia gaudichaudii. The structures were determined by spectral analysis which provided good agreement with the previously isolated gaudichaudi-one B(3).
Article
Three new caged tetraprenylated xanthones, named scortechinones A–C (1–3) were isolated from twigs of Garcinia scortechinii together with friedelin and stigmasterol. The scortechinone structures were elucidated by analysis of spectroscopic data and comparison of the NMR data with those of gaudichaudione H (4). The antibacterial activity against methicillin-resistant Staphylococcus aureus was evaluated.
Article
A further demonstration of the value of "biomimetically" inspired synthetic strategies toward natural products is provided by the title reactions that were developed for the construction of 4-oxatricyclo[4.3.1.0]decan-2-one systems from prochiral aromatic precursors. This biomimetic cascade was applied to the synthesis of 1-O-methylforbesione (2) from the prenylated xanthone 1 in one pot.
Article
New rearranged polyprenylxanthones, namely garcibracteatone, neoisobractatins A and B, and xerophenone C were isolated from the leaves and bark of a vietnarnese Garcinia, Garcinia bracteata, together with 5-O-methylxanthone V-1, bracteaxanthones I and II, and the known nemorosonol and simple xanthones. Neoisobractatins A and B exhibit a significant cytotoxic activity on KB cells. A biogenetic hypothesis is proposed, which explains the possible origin of these so-called cage-xanthanoids. (c) 2005 Elsevier Ltd. All rights reserved.
Chapter
IntroductionPolycyclic Polyprenylated PhloroglucinolsPolyprenylated XanthonesReferences
Article
Four new compounds, oliganthins A-D (1-4), and one known caged xanthone gaudichaudione H (5) were isolated from the stems of Garcinia oligantha. The structures of the new compounds were elucidated by spectroscopic evidences. All of the five compounds were evaluated for their apoptosis-inducing effects using HeLa-C3 cells which have been genetically engineered to produce a fluorescent biosensor capable of detecting caspase-3 activation. All of them induced cell apoptosis at 10 μM or lower concentrations. The apoptotic activity of oliganthins A, B and gaudichaudione H were further confirmed by detecting the cleavage of PARP, which is the substrate of activated caspase-3, in these compounds-treated cells using the method of Western blot. Moreover, the values of IC(50) were measured for all five compounds on HeLa cells using the MTT assay. Among them, gaudichaudione H had the lowest IC(50) value of 0.90 μM, while the other four new compounds had IC(50) values of 1.58, 1.52, 4.15, and 7.82 μM, respectively. These results show that gaudichaudione H has the strongest apoptosis-inducing effect and cell growth inhibition effect among these xanthones and it may have the potential to be developed into a new anticancer agent.
Article
Prenylated caged xanthones are "privileged structure" characterized by the presence of the unusual 4-oxo-tricyclo[4.3.1.0(3,7)]dec-8-en-2-one scaffold. The natural sources of these compounds confines mainly in the Garcinia genus in the family of Guttiferae. Gambogic acid is the most abundant substance and most of the studies have been done on this compound, particularly as a new potential antitumor agent. The history, sources, structural diversity, and biological activities of these compounds are covered. This review is written with the intention to provide additional aspects from what have been published of prenylated caged xanthones, including history, sources, structural diversity, and biological activities. This review has been compiled using information from a number of reliable references mainly from major databases including SciFinder, ScienceDirect, and PubMed. More than 120 prenylated caged xanthones have been found in the plant genera Garcinia, Cratoxylum, and Dascymaschalon. These compounds exhibited various potentially useful biological activities such as anticancer, anti-HIV-1, antibacterial, anti-inflammatory, and neurotrophic activities. Prenylated caged xanthones, both naturally occurring and synthetic analogues, have been identified as promising bioactive compounds, especially for anticancer agents. Gambogic acid has been demonstrated to be a highly valuable lead compound for antitumor chemotherapy. The structure activity relationship (SAR) study of its analogues is still the subject of intensive research. Apoptosis cytotoxic mechanism has been identified as the major pathway. Research on the delineation of the in-depth mechanism of action is still on-going. Analogues of gambogic acid had been identified to be effective against a rare and special form of liver cancer, cholangiocarcinoma for which currently there is no chemotherapeutic treatment available.
Article
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A new caged xanthone (1), a new prenylxanthone (2), seven known xanthones, and a known sterol glucoside were isolated from the stems of Cratoxylum cochinchinense, collected in Vietnam. Compounds 1 and 2 were determined structurally by analysis of their spectroscopic data. In addition, five new (10 and 16-19) and eight known prenylated xanthone derivatives were synthesized from the known compounds α-mangostin (3) and cochinchinone A (6). Several of these substances were found to be cytotoxic toward HT-29 human colon cancer cells, with the most potent being 3,6-di-O-acetyl-α-mangostin (8, ED50, 1.0 μM), which was tested further in an in vivo hollow fiber assay, but found to be inactive at the highest dose used (20 mg/kg; ip). Of the substances evaluated in a NF-κB p65 inhibition assay, 1,3,7-trihydroxy-2,4-diisoprenylxanthone (5) exhibited the most potent activity (IC50, 2.9 μM). In a mitochondrial transmembrane potential assay, two new compounds, 1 (IC50, 3.3 μM) and 10 (IC50, 1.4 μM), and two known compounds, 3 (α-mangostin, IC50, 0.2 μM) and 11 (3,6-di-O-methyl-α-mangostin, IC50, 0.9 μM), were active. A preliminary analogue development study showed that 3,6-diacetylation and 6-benzoylation both slightly increased the cytotoxicity of α-mangostin (3), whereas methylation reduced such activity. In contrast, neither acetylation, benzoylation, nor methylation enhanced the cytotoxicity of cochinchinone A (6).
Article
A new biflavonoid (1), a new xanthone enantiomer (2), five new caged xanthones (3-7), and several known compounds were isolated from the stem bark of Garcinia lateriflora, collected in Indonesia. The structures of the new compounds were determined by analysis of spectroscopic data, and the absolute configuration of the caged xanthones was shown for the first time at carbons 5, 7, 8, 8a, 10a, and 27, by analysis of COSY and NOESY NMR and ECD spectra. The biflavonoids exhibited proteasome inhibitory activity, and the known compound, morelloflavone (8) was found to have the greatest potency (IC(50) = 1.3 muM). The caged xanthones were cytotoxic towards HT-29 cells, with the known compound, morellic acid (10) being the most active (ED(50) = 0.36 muM). However, when tested in an in vivo hollow fiber assay, it was inactive at the highest dose tested (20 mg/kg).
Article
To study the chemical constituents of the twigs of Garcinia xipshuanbannaensis. The compounds were isolated by column chromatography with silica gel, RP-18 and Sephadex LH-20, and their structures were elucidated by spectroscopic analysis. Fifteen compounds were obtained and identified, which were bannaxanthone E (1), xanthochymol (2), isoxanthochymol (3), cycloxanthochymol (4), osajaxanthone (5), gentisein (6), mangostinone (7), kaempferol (8), quercetin (9), vitexin (10), 2"-O-acetylvitexin (11), 3-acetoxyoleanolic acid (12), (-)-epicatechin (13), beta-sitosterol (14) and daucosterol (15), respectively. Compounds 4-9 and 11-13 were isolated from the plant and compounds 11-13 were obtained from the genus Garcinia for the first time.
Article
Twelve new xanthones (1-12), a pair of new natural products (13 and 14), and 18 known related compounds were isolated from the resin of Garcinia hanburyi. The structures of 1-14 were elucidated by detailed spectroscopic analyses. A cytotoxic assay of the isolated compounds revealed that, with the exception of 2, these compounds were active against the HeLa tumor cell line.
Article
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3,10-Dihydroxydielmentha-5,11-diene-4,9-dione, a diterpenoid (C20H28O4) from Callitris macleayana heartwood, is shown by degradation, by both one- and two-dimensional high-field n.m.r. exploration, and by X-ray crystallographic analysis to have a unique carbon skeleton formally based upon the Diels-Alder self- dimerization of a p- menthadienone.
Article
Gambogic acid has been shown to have the constitution XXIVa. This structure has been established mainly by the study of the NMR spectra of gambogic acid, its derivatives, and a new series of transformation products called the gamboginates. The gamboginates are produced from gambogic acid and dimethyl gambogate by treatment with acid.Gambogic acid is shown to be closely related to morellin (XXa), and these two natural products are of novel structure.In accordance with the suggestion made by Dyson and Rigby,10 we use the name gambogic acid rather than α-gambogic acid as used previously.
Article
Synthesis of 5, 5-dimethyl- 7-methoxy-4 -oxatricyclo[4,3,1,0(3,7)]- decan-2-one 3a, a novel heterocyclic ring system present in morellin 1, and its 3-substituted derivatives 3b-e, is described from the Diels-Alder adducts 7, available from 1-methoxycyclohexa-1,4-dienes 4. Two routes, which involved the halocyclisation and the oxidative addition, were investigated for the conversion of the adducts 7 into 3. While the halocyclisation method resulted in mixtures, excellent yields of the target molecule were obtained by the second method. Solvolysis of the bromoether 9 resulted in a mixture of rearranged products 10, 13, 15 and 16.
Article
The isolation of gambogic acid is described. Reactions of gambogic acid are discussed and it is shown that some reactions involve isomeric change in the molecule. The possible relationship of gambogic acid to morellin is considered, the substitution pattern being examined in detail, and a structure is assigned which is consistent with much of the known chemistry of gambogic acid.
Article
Four new isoprenylated xanthones, morusignins F (1), F (2), G (3), and H (4) were isolated from the root bark of Morus insignis Bur. (Moraceae), collected in Paraguay. The structures of morusignins E-H were shown to be 1-4, respectively, on the basis of spectroscopic data.
Article
Three xanthone derivatives, gambogic acid, isogambogic acid and isomorellinol, were isolated from the dried latex of Garcinia hanburyi. Two of them, isogambogic acid and isomorellinol, are new. Determinations of the structures and stereochemistry were achieved independently by a series of NMR experiments including COSY, ROESY, HMQC, HMBC and selective INEPT. Isolation of isomorellinol from G. hanburyi provided important chemical evidence to link this species to G. morella. The presence of gambogic acid and isogambogic acid, however, demonstrated the difference between these two species. Cytotoxic evaluation of these isolates revealed that all three were active against KB and drug-resistant KB-V1 cell lines.
Article
A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
Article
Eleven novel cytotoxic xanthones, gambogin, morellin dimethyl acetal, isomoreollin B, moreollic acid, gambogenic acid, gambogenin, isogambogenin, desoxygambogenin, gambogenin dimethyl acetal, gambogellic acid and hanburin were isolated together with four known xanthones, gambogic acid, isomorellin, morellic acid and desoxymorellin, from the dry latex of Garcinia hanburyi. The structures were elucidated by a detailed spectroscopic analysis.
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