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Moluccensins H-J, 30-Ketophragmalin Limonoids from Xylocarpus moluccensis
Abstract
Three new phragmalin limonoids, moluccensins H-J (1-3), were isolated from seed kernels of the cedar mangrove, Xylocarpus moluccensis. Their structures were established by extensive spectroscopic analysis. Compound 2 displayed weak antibacterial activity against Staphylococcus hominis and Enterococcus faecalis.
... The H-17 resonance showed correlations with the C-18 (δ C 14.4), C-12 (δ C 26.0), C-13(δ C 37.9), and C-14 (δ C 67.6) resonances in the HMBC spectrum. Ring D comprised a δ-lactone moiety with the C-16 lactone carbonyl resonance (δ C 169. 4) showing The chemical shifts for C-8 and C-14 indicated the presence of an 8,14-epoxide. Ring A was rearranged as shown by the characteristic carbomethoxy resonance at δ H 3.76 (3H, s, 7-OMe). ...
... 12 The typical H-3/H-2/H-30 coupled system was indicated in the COSY spectrum by resonances at δ H 5.20 (1H, d, J = 10.8 Hz, H-3), 3.08 (1H, dd, J = 10.8, 2.4 Hz, H-2), and 5.34 (1H, d, J = 2. 4 Hz, H-30). Ester groups were present at C-3β and C-30α and were found to be (2S)-methylbutyryloxy and isobutyryloxy, respectively, as in compounds 1 and 2. The H-2 and H-30 resonances showed a correlation in the HMBC spectrum with a keto carbonyl resonance at δ C 213.6, which was assigned as C-1. ...
Nine triterpenoid derivatives were isolated from the heartwood of Xylocarpus rumphii and were identified as xylorumphiins E (1), C (2), L (3), and M-R (4-9). Compounds 4-9 have a hemiacetal group in the triterpenoid side chain, making them impossible to purify. Purification was achieved after acetylation and subsequent separation of the epimeric mixtures of acetates; however differentiaition of the R and S epimers was not possible using standard NMR techniques. In one case, the relative configuration of a remotely located stereocenter with respect to the stereocenters in the main skeleton was unambiguously determined using residual dipolar couplings. Dipolar couplings were collected from the sample oriented in compressed poly(methyl methacrylate) gels swollen in CDCl3. In another case, the relative configuration was determined using 1D selective quantitative NOE experiments. Xylorumphiin K (10), xyloccensin E, taraxer-14-en-3β-ol, (22S)-hydroxytirucalla-7,24-diene-3,23-dione, and 25-hydroxy-(20S,24S)-epoxydammaran-3-one were isolated from the bark of the same plant. Compounds 3-10 are new compounds. Compounds 1-6 and xyloccensin E were tested at one concentration, 1 × 10(-5) M, in the NCI59 cell one-dose screen but did not show significant activity.
... The H-17 resonance showed correlations with the C-18 (δ C 14.4), C-12 (δ C 26.0), C-13(δ C 37.9), and C-14 (δ C 67.6) resonances in the HMBC spectrum. Ring D comprised a δ-lactone moiety with the C-16 lactone carbonyl resonance (δ C 169. 4) showing The chemical shifts for C-8 and C-14 indicated the presence of an 8,14-epoxide. Ring A was rearranged as shown by the characteristic carbomethoxy resonance at δ H 3.76 (3H, s, 7-OMe). ...
... 12 The typical H-3/H-2/H-30 coupled system was indicated in the COSY spectrum by resonances at δ H 5.20 (1H, d, J = 10.8 Hz, H-3), 3.08 (1H, dd, J = 10.8, 2.4 Hz, H-2), and 5.34 (1H, d, J = 2. 4 Hz, H-30). Ester groups were present at C-3β and C-30α and were found to be (2S)-methylbutyryloxy and isobutyryloxy, respectively, as in compounds 1 and 2. The H-2 and H-30 resonances showed a correlation in the HMBC spectrum with a keto carbonyl resonance at δ C 213.6, which was assigned as C-1. ...
Eleven compounds were isolated from the heartwood of X. rumphii and were identified as xylorumphins A and C (1 and 2), xylorumphiin C (3), xylorumpholides A-G (4 – 10) and odoratone (11). Compounds 4 – 10 have a hemiacetal group which opens and closes in solution making it impossible to purify. Acetylation enabled separation of the α and β forms. Column chromatographic separation of the acetylated fraction of impure 4 – 10 led to the isolation of one acetylated derivative of 4 (4a), four acetylated derivatives of 5 (5a-d), two acetylated derivatives of 6 (6a and 6b), one acetylated derivative of 8 (8a), two acetylated derivatives of 9 (9a and 9b) and one acetylated derivative of 10 (10a). In addition, five compounds were isolated from the bark of the same plant and were identified as xylorumphin B (12), xyloccensin E (13), taraxer-14-en-3β-ol (14), 22e-hydroxytirucalla-7,24-dien-3,23-dione (15) and 3-oxo-(20S,24S)-epoxydammaran-25-ol (16). Compounds 1, 2, 4 – 10 and 12 have not been described previously. Chemical constituents from the Xylocarpus genus are reported to exhibit several biological activities such as antidiarrhoeal [1], antimalarial [2], anti-inflammatory [3] and insect antifeedant [4], and the aqueous extract of X. granatum is reported to express significant antifilarial activity [5]. Eight compounds, 1 – 6, 4a and 13 were tested at one concentration, 1 × 10 – 5 M, against several leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast cancer cell lines. The compounds did not meet activity criteria in the one-dose NCI59 cell test for further testing. References: [1] Shen LR, Guo D, Yu YM et al. Chem Biodivers 2009; 6: 1293 – 1308 [2] MacKinnon S, Durst T, Arnason JT et al. J Nat Prod 1997; 60: 336 – 341 [3] Sarigaputi C, Sommit D, Teerawatananond T et al. J Nat Prod 2014; 77: 2037 – 2043 [4] Champagne DE, Koul O, Isman MB et al. Phytochemistry 1992; 31: 377 – 394 [5] Zaridah MZ, Idid SZ, Omar AW et al. J Ethnopharmacol 2001; 78: 79 – 84
... Triterpenoids: limonoids [190,247,248,[253][254][255][256][257][258][259][260][261], tirucallane-type triterpenoids [260]; Protein, minerals and fatty acids [262]. ...
... The limonoids of X. moluccensis seeds have been investigated for insecticidal, pesticidal and anti-feedant effects, with many of them being found active [254,256,258,260,261]. Some of these applications have been patented [263,264]. ...
Diarrhoea is a common disease which causes pain and may be deadly, especially in developing countries. In Bangladesh, diarrhoeal diseases affect thousands of people every year, and children are especially vulnerable. Bacterial toxins or viral infections are the most common cause of the disease. The diarrhoea outbreaks are often associated with flood affected areas with contaminated drinking water and an increased risk of spreading the water-borne disease. Not surprisingly, plants found in the near surroundings have been taken into use by the local community as medicine to treat diarrhoeal symptoms. These plants are cheaper and more easily available than conventional medicine. Our question is: What is the level of documentation supporting the use of these plants against diarrhoea and is their consumption safe? Do any of these plants have potential for further exploration? In this review, we have choosen seven plant species that are used in the treatment of diarrhoea; Diospyros peregrina, Heritiera littoralis, Ixora coccinea, Pongamia pinnata, Rhizophora mucronata, Xylocarpus granatum, and Xylocarpus moluccensis. Appearance and geographical distribution, traditional uses, chemical composition, and biological studies related to antidiarrhoeal activity will be presented. This review reveals that there is limited scientific evidence supporting the traditional use of these plants. Most promising are the barks from D. peregrina, X. granatum and X. moluccensis which contain tannins and have shown promising results in antidiarrhoeal mice models. The leaves of P. pinnata also show potential. We suggest these plants should be exploited further as possible traditional herbal remedies against diarrhoea including studies on efficacy, optimal dosage and safety.
... Further literacy revealed that the planar structure of 3 was similar to that tabulvelutin B [16], except for the presence of an additional O-acetyl at C-30. Limonoids have a prototypical structure derived from a 4,4,8-trimethyl-17-furanylsteroid skeleton, leading to the stereochemically homogeneous [17]. The similar NOE interactions suggested that 3 possessed the same relative orientation as mexicanolide derivatives, such as compounds 1 and 2. The additional stereocenters at C-1 and C-30, as well as the non-protonated carbons at C-2 and C-8, were adopted to be α-oriented as its analog, tabulvelutin B [16], based on observed NOESY cross-peaks between H-9/H 3 -19 (α-oriented) to 1-OH and H 3 -28 (β-oriented) to H-30. ...
A total of five new mexicanolides (1–5), namely alliaxylines A–E, together with two known limonoids 6 and 7, were isolated and identified from Dysoxylum alliaceum (Blume) Blume ex. A.Juss. (Meliaceae). The structures of these compounds were elucidated based on extensive spectroscopic analyses, including HR-ESI–MS, UV, IR, 1D, and 2D NMR, as well as theoretical stimulation of NMR shifts with the DP4 + algorithm. Consequently, this study aimed to examine cytotoxic activities of these compounds against MCF-7 and A549 cell lines. The results implied that compound 2 was the most potent against the two tested cells, with IC50 values of 34.95 ± 0.21 and 44.39 ± 1.03 µM.
... Another example is krishnolide A (58) [169]. From the latter, moluccensin I from the fruits moderately inhibited the growth of S. hominis and E. faecalis [170]. The limonoid catabolite dihydrofuranone 3-(1-hydroxyethyl)-2,2-dimethyl-4-butyrolactone (59) from the leaves of X. granatum is a strong repressor of the phytopathogenic fungi Blumeria graminis [171]. ...
Microbes such as the White Spot Syndrome Virus account for severe losses in the shrimp farming industry globally. This review examines the literature on the mangrove plants of Asia and the Pacific with antibacterial, antifungal, or antiviral activities. All of the available data published on this subject were collected from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and a library search from 1968 to 2022. Out of about 286 plant species, 119 exhibited antimicrobial effects, and a total of 114 antimicrobial natural products have been identified including 12 with MIC values below 1 µg/mL. Most of these plants are medicinal. The mangrove plants of Asia and the Pacific yield secondary metabolites with the potential to mitigate infectious diseases in shrimp aquaculture.
... Although, more than twenty novel limonoids have been recently isolated from seeds kernels of three Thai mangroves in genus Xylocarpus -X. granatum, X. moluccensis and X. rumphii [33][34][35][36], only two gedunin-type limonoids, 7deacetylgedunin (17) and 7-oxo-7-deacetoxygedunin (18) [37] displayed significant effective inhibition. Isolation method described by Ravangpai et al. [37] based on air-dried powder of plant material (X. ...
Limonoids are chemically classified on the basis of the four rings, marked as A, B, C and D in the intact triterpene nucleus with various oxidative modifications. The structural variations of limonoids found in Rutaceae species are lesser than in species of Meliaceae. Limonoids isolated from the plant family Meliaceae are more complex with very high degree of oxidation and structural rearrangements. Limonoids family exhibits a wide spectrum of biological properties, such as cytostatic, antimalarial, anti-inflammatory, antifeedant, antiviral, neuroprotective and a number of other activities like antimicrobial acitivity.
Phragmalin-type limonoids are highly complex natural products based on an unusual octahydro-1H-2,4-methanoindene cage. The absence of feasible routes to sufficiently functionalized methanoindene cage building blocks impedes the total synthesis of these natural products. We have developed a short and robust route to methanoindene cage compounds from the Hajos-Parrish ketone (HPK). Several stereoselective modifications of the HPK provided a substrate that underwent aldol reaction as a key step for the cage formation.
Nature has bestowed us with abundant bioactive/drug molecules for various uses in our everyday life. One such group of plant specialized molecules is limonoids, which are structurally characterized as 4,4,8-trimethyl-17-furanyl steroidal skeleton. Limonoids are well known for their various biological activities such as potent anti-feedent, anti-cancer, anti-inflammatory, insecticidal, anti-diabetic, anti-viral, anti-microbial etc. These tetranortriterpenes are highly oxygenated and structurally diversified molecules majorly found in Meliaceae and Rutaceae and less frequently in the Cneoraceae families in the plant kingdom. Many of these plants have been used in traditional medicine from ages. One of the well-known limonoid, azadirachtin A is highly valued and widely popular for its outstanding insecticidal properties. Till date, nearly 2500 limonoids with over 35 unique carbon frameworks have been observed. In recent times, these molecules have dig a great interest among researchers due to their myriad biological properties. With the advancement of analytical techniques, the limonoid research is aced to explore more different molecules from their sources. In our review we cover all the Meliaceous limonoids isolated during July 2010 to Dec 2020. We found over 1502 new limonoids, which are reported from various Meliaceae plants after Jun 2010. We have classified them based on their skeletal structure rearrangements and functional groups into various classes such as protolimonoids, Apoprotolionoid, Azadirone, Vilasinin, Cedrelone, Havanensin, Trichilin, Nimbin, Salannin, Azadirachtin, Nimbolidin, Nimbolinin, Obacunol, Evodulone, Trijugin, Cipadesin, Andirobin, Mexicanolide, Phragmalin, Khayanolide, Preieurianin, Aphanamixoid, Nor Limonoid and N-containing derivatives. Further we have discussed their biological activities in detail.
Nature has bestowed us with abundant bioactive/drug molecules for various uses in our everyday life. One such group of plant specialized molecules is limonoids, which are structurally characterized as 4,4,8-trimethyl-17-furanyl steroidal skeleton. Limonoids are well known for their various biological activities such as potent anti-feedent, anti-cancer, anti-inflammatory, insecticidal, anti-diabetic, anti-viral, anti-microbial etc. These tetranortriterpenes are highly oxygenated and structurally diversified molecules majorly found in Meliaceae and Rutaceae and less frequently in the Cneoraceae families in the plant kingdom. Many of these plants have been used in traditional medicine from ages. One of the well-known limonoid, azadirachtin A is highly valued and widely popular for its outstanding insecticidal properties. Till date, nearly 2500 limonoids with over 35 unique carbon frameworks have been observed. In recent times, these molecules have dig a great interest among researchers due to their myriad biological properties. With the advancement of analytical techniques, the limonoid research is aced to explore more different molecules from their sources. In our review we cover all the Meliaceous limonoids isolated during July 2010 to Dec 2020. We found over 1502 new limonoids, which are reported from various Meliaceae plants after Jun 2010. We have classified them based on their skeletal structure rearrangements and functional groups into various classes such as protolimonoids, Apoprotolionoid, Azadirone, Vilasinin, Cedrelone, Havanensin, Trichilin, Nimbin, Salannin, Azadirachtin, Nimbolidin, Nimbolinin, Obacunol, Evodulone, Trijugin, Cipadesin, Andirobin, Mexicanolide, Phragmalin, Khayanolide, Preieurianin, Aphanamixoid, Nor Limonoid and N-containing derivatives. Further we have discussed their biological activities in detail.
Nature has bestowed us with abundant bioactive/drug molecules for various uses in our everyday life. One such group of plant specialized molecules is limonoids, which are structurally characterized as 4,4,8-trimethyl-17-furanyl steroidal skeleton. Limonoids are well known for their various biological activities such as potent anti-feedent, anti-cancer, anti-inflammatory, insecticidal, anti-diabetic, anti-viral, anti-microbial etc. These tetranortriterpenes are highly oxygenated and structurally diversified molecules majorly found in Meliaceae and Rutaceae and less frequently in the Cneoraceae families in the plant kingdom. Many of these plants have been used in traditional medicine from ages. One of the well-known limonoid, azadirachtin A is highly valued and widely popular for its outstanding insecticidal properties. Till date, nearly 2500 limonoids with over 35 unique carbon frameworks have been observed. In recent times, these molecules have dig a great interest among researchers due to their myriad biological properties. With the advancement of analytical techniques, the limonoid research is aced to explore more different molecules from their sources. In our review we cover all the Meliaceous limonoids isolated during July 2010 to Dec 2020. We found over 1502 new limonoids, which are reported from various Meliaceae plants after Jun 2010. We have classified them based on their skeletal structure rearrangements and functional groups into various classes such as protolimonoids, Apoprotolionoid, Azadirone, Vilasinin, Cedrelone, Havanensin, Trichilin, Nimbin, Salannin, Azadirachtin, Nimbolidin, Nimbolinin, Obacunol, Evodulone, Trijugin, Cipadesin, Andirobin, Mexicanolide, Phragmalin, Khayanolide, Preieurianin, Aphanamixoid, Nor Limonoid and N-containing derivatives. Further we have discussed their biological activities in detail.
Seven new limonoids, named krishnolides E–K (1–7), including three khayanolides, two mexicanolides, a derivative of trangmolin A, and an andirobin, were isolated from seeds of the Indian Krishna mangrove, Xylocarpus moluccensis. The structures of these limonoids were established by HRESIMS, extensive NMR investigations, and X-ray crystallography. Most notably, the absolute configurations of 1, 5, 6, and 7 were unequivocally determined by single-crystal X-ray diffraction analyses (Cu Kα). Krishnolide F (2) exhibited significant agonistic effects on human pregnane-X-receptor (hPXR) at the concentration of 10.0 μM. Molecular docking revealed that 2 could bind a helix near the region of the Helix 12 of hPXR. Polar contribution could be electrostatic effects from the formation of two stable protein-ligand hydrogen bonds between Gln285/1-OH and His407/1-OH, respectively. This is the first report of agonistic effects of a khayanolide-type limonoid on hPXR.
Human pregnane–X–receptor (hPXR) is considered to be the key target for the treatment of cholestasis and liver injury. Agonists of hPXR are potential drug leads. Potent and selective inhibitors of human carboxylesterase 2 (hCES2) could be utilized to alleviate the toxicity induced by ester drugs. In this work, fifteen new tetranortriterpenoids with structure diversity, named thaigranatins F-T (1-15), including four limonoids containing a C1–O–C29 bridge (1-4), four mexicanolides (5-8), three phragmalins (9-11), two limonoids belonging to the small group of trichiliton A (12-13), and two apotirucallanes (14-15), were isolated from seeds of the Thai mangrove, Xylocarpus granatum. The structures of these compounds were established by high resolution-electrospray ionization mass spectroscopy, extensive NMR spectroscopic investigations, single-crystal X-ray diffraction analyses, and the comparison of experimental electronic circular dichroism spectra. Most notably, thaigranatins L (7) and P (11) exhibited agonistic effects on hPXR at the concentration of 10.0 μM and 10.0 nM, respectively, whereas thaigranatins J (5), M (8), and T (15) showed inhibitory activities against hCES2 with IC50 values of 6.63, 11.35, and 5.05 μM, respectively. The 8α,30α-epoxy moiety of mexicanolide and the Δ8,14 double bond of phragmalin are pivotal for agonistic effects of these limonoids on hPXR, whereas the 6-OAc group of mexicanolide is crucial for its inhibitory activity against hCES2. Additionally, the flexible C-17-side-chain with appropriate hydroxy groups is considered to be important for the inhibitory activity of apotirucallane against hCES2.
Nine new limonoids, named thaixylomolins S–Z (1–8) and 2-O-acetylthaixylomolin Z (9), were isolated from seeds of the mangrove, Xylocarpus moluccensis, collected in the mangrove swamp of Trang Province, Thailand. Thaixylomolin S (1) is the fourth member of the khayalactone class of limonoids containing a hexahydro-2H-2,5- propanocyclopenta[b]furan motif. Thaixylomolins T–Y (2–7) are structurally diverse mexicanolides; whereas thaixylomolin Z (8) and 2-O-acetylthaixylomolin Z (9) are phragmalin 8,9,30-orthoesters. The structures of these compounds were established by HRESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of thaixylomolins S (1), U (3), and Z (8) were unambiguously established by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation; whereas that of 2-O-acetylthaixylomolin Z (9) was determined to be the same as that of thaixylomolin Z (8) by the accurate fit of their experimental electronic circular dichroism spectra. Thaixylomolin S (1), featuring the presence of a 30-(2′-methyl)butyryloxy group, is the first limonoid of the khayalactone class, whose constitution and absolute configuration are unequivocally determined by X-ray crystallography. The inhibitory activities of all the compounds, except for the epimers 4, were assayed against human carboxylesterase 2. All the tested compounds exhibited inhibition rates in the range of 16–65% at the concentration of 100.0 μM.
Twenty-four new limonoids (1–24), named hainanxylogranins A–X, were isolated from leaves and barks of the Hainan mangrove, Xylocarpus granatum, together with a known compound, tabulvelutin B (25). The structures of these compounds were established by high resolution electrospray ionization mass spectroscopy (HRESIMS), extensive NMR spectroscopic investigations, single-crystal X-ray diffraction analyses, and the comparison of experimental electronic circular dichroism (ECD) spectra. Most notably, the absolute configurations of seven compounds, viz., 1, 2, 6, 16, 17, 22, and 25, were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation. Compounds 1–4 belong to a unique group of mexicanolides containing a C3–O–C8 bridge and a C-17 substituted γ(21)-hydroxybutenolide moiety, whereas 5–9 are mexicanolides comprising a C1–O–C8 bridge. Compounds 10–16 are typical mexicanolides, among which 14 and 15 contain a C-17 substituted γ(23)-hydroxybutenolide moiety. Compounds 17 and 18 are phragmalin 8,9,30-orthoesters, whereas 19 and 20 are phragmalin 1,8,9-orthoesters. Compound 21 consists of a C1–O–C29 bridge, while 22–24 are derivatives of azadirone. The inhibitory activities of 1, 5–8, 11, 17, 19, 21–23, and 25 against human carboxylesterase 2 (CES2) were assayed. All the tested compounds exhibited inhibition rates of 30-64% at the concentration of 100.0 µM.
Covering: 2015. Previous review: Nat. Prod. Rep., 2016, 33, 382-431This review covers the literature published in 2015 for marine natural products (MNPs), with 1220 citations (792 for the period January to December 2015) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1340 in 429 papers for 2015), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.
Eight new khayanolides, named thaixylomolins G-N (1-8), two new phragmalins (9 and 10), and two new mexicanolides (11 and 12) were obtained from the seeds of the Trang mangrove plant Xylocarpus moluccensis. The absolute configurations of these limonoids, except for the stereocenter at C-6 of 11 and 12, were assigned by experimental and TDDFT calculated electronic circular dichroism spectra. The khayanolides may be classified into two subclasses, one of which has a C-2 carbonyl and a 3β-acetoxy group, whereas the other possesses a 2β-acetoxy and a C-3 carbonyl function. Khayanolides, rearranged phragmalin-type limonoids, are reported for the first time from plants of the mangrove genus Xylocarpus. The structure of moluccensin J, a known 30-ketophragmalin containing a Δ(8(14)) double bond, was revised to be a khayanolide, named thaixylomolin K. The antiviral activities of the isolates against pandemic influenza A virus (subtype H1N1) were tested by the assay of cytopathic effect inhibition. Three khayanolides, viz., thaixylomolins I, K, and M, exhibited moderate anti-H1N1 activities. The most potent one, thaixylomolin I (IC50 = 77.1 ± 8.7 μM), showed stronger inhibitory activity than that of the positive control, ribavirin (IC50 = 185.9 ± 16.8 μM).
Three new limonoids, named thaixylomolins D-F (1-3), were obtained from the seeds of a Thai true mangrove, Xylocarpus moluccensis. The structures of these compounds were identified by extensive NMR and HR-ESIMS/MS investigations. They are further additions to the small group of phragmalins with a C-30 carbonyl moiety, among which thaixylomolins D-E (1-2) contain a D8,14 double bond, whereas thaixylomolin F (3) possesses conjugated δ8,9 and δ14,15 double bonds. © 2013 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
In this study, limonoids isolated from Xylocarpus plants were tested for their in vitro anti-inflammatory effects. The results demonstrated that only 7-deacetylgedunin (1), a gedunin-type limonoid, significantly inhibited lipopolysaccharide- and interferon-γ-stimulated production of nitric oxide in murine macrophage RAW 264.7 cells. The suppression of nitric oxide production by 1 was correlated with the downregulation of mRNA and protein expression of inducible nitric oxide synthase. Mechanistic studies revealed that the transcriptional activity of nuclear factor-κB, IκBα degradation, and the activation of mitogen-activated protein kinases, stimulated with lipopolysaccharide and interferon-γ, were suppressed by 1.
Georg Thieme Verlag KG Stuttgart · New York.
Seven new limonoids, namely, xylorumphiins E-J (1-2 and 4-7) and 2-hydroxyxylorumphiin F (3), along with three known derivatives (8-10), were isolated from the seeds of Xylocarpus rumphii. 2-Hydroxyxylorumphiin F (3) and xylorumphiin I (6) displayed moderate inhibitory activity against nitric oxide production from lipopolysaccharide-activated macrophages with IC50 values of 24.5 and 31.3 μM, respectively.
Godavarin K (1), a new limonoid with an oxygen bridge between C(1) and C(29), was obtained from seeds of an Indian mangrove, Xylocarpus moluccensis, together with a known tetranortriterpene, 6-de(acetyloxy)-7-deacetylchisocheton compound E (=(5α,7α,13α,17α)-7-hydroxy-4,4,8-trimethyl- 3-oxocarda-1,14-dienolide; 2). The structure of godavarin K was established on the basis of spectroscopic data. In addition, the confusion of 1H- and 13C-NMR data for compound 2 in previous literature was clarified. Copyright
Ten limonoids, named granatumins L-U (1-10, resp.), were isolated from the seeds of an Indian mangrove, Xylocarpus granatum, collected in the estuary of Krishna, Andhra Pradesh. The structures of these compounds were established on the basis of spectroscopic data. The relative configuration of granatumin L (1) was confirmed by a single-crystal X-ray diffraction analysis. Granatumins L-T (1-9, resp.) belong to the small group of limonoids with an oxygen bridge between C(1) and C(29), while granatumin U (10) is a 28-Me-oxidized mexicanolide. This is the first report of limonoids with an O-bridge between C(1) and C(29) from the Indian X. granatum. The pronounced structural diversity of limonoids from this mangrove might originate from environmental factors.
Swietemahalactone (1), a novel rearranged phragmalin-type limonoid, was isolated from Swietenia mahagoni. The structure of 1 was established on the basis of extensive spectroscopic and X-ray crystallographic methods. Swietemahalactone exhibited antibacterial activity using the agar diffusion method. The key biogenetic pathway of 1 is the semipinacol rearrangement.
The title compound (systematic name: methyl 2-{(1R,2R)-2-[(1aS,4S,4aS,8aS)-4-(furan-3-yl)-4a-methyl-8-methylene-2-oxooctahydrooxireno[2,3-d]isochromen-7-yl]-2,6,6-trimethyl-5-oxocyclohex-3-en-1-yl}acetate), C27H32O7, was isolated from X. moluccensis seeds from Thailand. The conformations of the six-membered rings are distorted half-chair, chair and half-chair for the isolated cyclohexane, fused cyclohexane and lactone rings, respectively. In addition, the lactone ring bears in an equatorial orientation an essentially planar furan ring (r.m.s. deviation = 0.004 Å), which forms an angle of 63.87 (13)° with the mean plane defined by the ten atoms of the two fused six-membered rings (r.m.s. deviation = 0.213 Å). The absolute configuration was fixed on the basis of literature data.
Covering: 2010. Previous review: Nat. Prod. Rep., 2011, 28, 196. This review covers the literature published in 2010 for marine natural products, with 895 citations (590 for the period January to December 2010) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1003 for 2010), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.
Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. Aberrations in osteoclast differentiation and activity contribute to osteopenic disease. Osteoclasts differentiate from monocyte/macrophage progenitors, a process that is initiated by the interaction between receptor activator of NF-κB (RANK) and its ligand, RANKL. In this study, we identified 7-oxo-7-deacetoxygedunin (7-OG), a gedunin type limonoid from seeds of the mangrove Xylocarpus moluccensis, as a potent inhibitor of osteoclastogenesis. Additionally, 7-OG showed strong anti-osteoclastogenic activity with low cytotoxicity against the monocyte/macrophage progenitor cell line, RAW264.7. The IC50 for anti-osteoclastogenic activity was 4.14μM. Treatment with 7-OG completely abolished the appearance of multinucleated giant cells with tartrate-resistant acid phosphatase activity in RAW264.7 cells stimulated with RANKL. When the expression of genes related to osteoclastogenesis was investigated, a complete downregulation of NFATc1 and cathepsin K and a delayed downregulation of irf8 were observed upon 7-OG treatment in the presence of RANKL. Furthermore, treatment with this limonoid suppressed RANKL-induced activation of p38, MAPK and Erk and nuclear localization of NF-κB p65. Taken together, we present evidence indicating a plant limonoid as a novel osteoclastogenic inhibitor that could be used for osteoporosis and related conditions.
Some of the important naturally occurring limonoids from Meliaceae discovered in the last six decades, from 1942 to June 30, 2010, and their various bioactivities, are discussed. The cedrelone-class limonoids are characterized as the 5,6-enol-7-one derivatives and Burke et al. presented the chemical correlation of anthothecol with hirtin. Under mildly acid conditions, the first stage of the ring-opening of havanensin gives a 15-hydroxy-14- carbonium ion, which then either undergoes Wagner-Meerwein rearrangement or loses a proton to give a 15-ketone enolate and involves participation of the oxygenated function at C-7. The photooxidation of salannin and nimbin by UV light in the presence of oxygen led to more polar unstable intermediates that rearranged on silica gel to two final products in which the furan ring had been oxidized to isomeric hydroxybutenolides.
A new andirobin, thaimoluccensin A (1), and two new phragmalin-type limonoids, thaimoluccensins B (2) and C (3), were isolated from seeds of a Thai mangrove plant, Xylocarpus moluccensis, together with eight known compounds. The structures of these compounds were elucidated on the basis of spectroscopic data. Only 7-deacetylgedunin (7), a gedunin-type limonoid, exhibited significant inhibitory activity against nitric oxide production from activated macrophages with IC(50) value less than 10 μM, suggesting that the compound has anti-inflammatory activity.
Four new mexicanolide limonoids, named xylorumphiins A-D (1-4), were isolated from the seed kernels of Xylocarpus rumphii, together with three known limonoids. Their structures and configurations were established on the basis of spectroscopic data.
A novel tetranortriterpenoid and two dihydrocinnamic acid derivatives were obtained from the wood of Hortia colombiana. Their structures were elucidated by detailed NMR investigations and the relative configurations established by Difference NOE experiments. In addition, alloxanthoxyletin, nerolidol, epoxynerolidol, three known dihydrocinnamic acid derivatives and two amides were isolated. Detailed analysis of NMR data of Hortiolide A, whose structure was previosly established by X ray, are also provided.
We have studied various factors involved in the optimal use of a tetrazolium (MTT) based colorimetric assay for cell growth and chemosensitivity. The assay is dependent on the ability of viable cells to metabolise a water-soluble tetrazolium salt into a water-insoluble formazan product. We have found that DMSO is the best solvent for dissolving the formazan product, especially where a significant amount of residual medium is left in the wells of the microtitre tray used for the assay. A reaction occurs between medium and a solution of MTT formazan in DMSO which changes the shape of the absorbance spectrum of the solution. The resulting optical density is not however greatly dependent upon the volume of added medium in the range 1-10 microliters. Between 10 and 40 microliters of added medium results in a gradually lower optical density than that produced by the smaller volumes. Above 40 microliters, the optical density increases again due to turbidity as protein precipitation occurs. When cells are incubated with MTT, the resulting optical density of the formazan product is dependent upon both the concentration of MTT and the incubation time. The optical density is stable for several hours after solution of the formazan in DMSO. A linear relationship is seen between optical density and cell number for incubation times of 2, 4, 6 or 24 h with 20 microliters of MTT (5 mg ml-1) added to 200 microliters medium. We have adopted 4 h as the standard incubation time for the assay. Only a small amount of MTT formazan product can be detected in the growth medium of wells in which cells have been exposed to MTT. Comparative chemosensitivity data for EMT6 mouse tumour cells show good agreement between results obtained using the MTT assay and results based on total cell count after a fixed period of growth.
Biological activities of the salannin type of limonoids isolated from Azadirachta indica A. Juss were assessed using the gram pod borer Helicoverpa armigera (Hubner) and the tobacco armyworm Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae). Inhibition of larval growth was concomitant with reduced feeding by neonate and third instar larvae. All three compounds exhibited strong antifeedant activity in a choice leaf disc bioassay with 2.0, 2.3 and 2.8 microg/cm(2) of 3-O-acetyl salannol, salannol and salannin, respectively deterring feeding by 50% in S. litura larvae. In nutritional assays, all three compounds reduced growth and consumption when fed to larvae without any effect on efficiency of conversion of ingested food (ECI), suggesting antifeedant activity alone. No toxicity was observed nor was there any significant affect on nutritional indices following topical application, further suggesting specific action as feeding deterrents. When relative growth rates were plotted against relative consumption rates, growth efficiency of the H. armigera fed diet containing 3-O-acetyl salannol, salannol or salannin did not differ from that of starved control larvae (used as calibration curve), further confirming the specific antifeedant action of salannin type of limonoids. Where the three compounds were co-administered, no enhancement in activity was observed. Non-azadirachtin limonoids having structural similarities and explicitly similar modes of action, like feeding deterrence in the present case, have no potentiating effect in any combination.
For the metabolic engineering of bio-functional substances in Citrus, metabolic changes of limonoids were investigated in embryogenic cell cultures of Citrus and Fortunella. When embryogenic cells of Citrus and Fortunella were cultured for four weeks in the liquid subculture medium containing nomilin, most species converted nomilin to obacunone and limonin. In addition, calamin group limonoids were produced in Fortunella and Calamondin cells. Deacetylnomilin was produced from nomilin in the cells of C. ichangensis and its related species. Exogenously added limonin into medium was not metabolized. The embryoid formation in C.aurantium did not affect the limonoid metabolism. All cells cultured without the presence of nomilin or limonin did not generate any limonoids. Furthermore, transgenic C. sinensis cell harboring a chimeric limonoid UDP-glucosyltransferase (limonoid GTase) gene was generated. The conversion of limonin into limonin 17-β-D-glucopyranoside (LG) demonstrated an efficient assay system for the transgene.
Further examination of the timber of Xylocarpus moluccensis has given three new compounds, xyloccensins G, H and I. Structures are deduced for G an
The first synthesis of (±)-fraxinellonone and its short step conversion into (±)-fraxinellone and (±)-isofraxinellone is described. The synthesized compounds exhibited moderate insect-antifeeding activity against Spodoptera exigua H. (Boisduval) and ichthyotoxicity against killifish.
Chukvelutilides A–F (1-6), a new class of C-15-acyl phragmalin type limonoids, featuring a C-16/C-30 δ-lactone ring, were isolated from Chukrasia tabularis var. velutina. These compounds are suggested to possess a three- or four-carbon enolized acyl substituent at C-15 through a plausible biosynthetic origin. Their structures were elucidated by extensive spectroscopic means, and that of 1 was confirmed by single-crystal X-ray diffraction.
The methanol (MeOH) extract of the barks of Xylocarpus moluccensis, and different fractions of this extract were studied for antidiarrhoeal activity using castor oil-and magnesium sulphate-induced diarrhoea models in mice. At the doses of 250 and 500 mg/kg, the MeOH extract showed significant antidiarrhoeal activity in both models. The EtOAc fraction (EAF) and the residual MeOH fraction (RMF) exhibited similar activity using a dose of 250 mg/kg in both models. No antidiarrhoeal activity was observed with the chloroform fraction (CHF) at the test doses. When tested for antibacterial effect, the MeOH extract displayed moderate inhibitory activity against Escherichia coli, Vibrio cholera, Staphylococcus aureus, Staphylococcus epidermis, Shigella dysentery, Staphylococcus pyogenes, Salmonella typhi, Pseudomonas aeruginosa and Enterobacter aerogenes. While the CHF inhibited the growth of Escherichia coli, Vibrio cholerae, Shigella dysenteriae, Shigella sonnei, Staphylococcus epidermis, Staphylococcus pyogenes and Pseudomonas aeruginosa, the EAF was active against all test organisms except Vibrio cholera and Staphylococcus epidermis. The RMF inhibited the growth of all the test organisms with moderate zone of inhibition. On the basis of these findings, it can be assumed that Xylocarpus moluccensis could be a potential source for novel 'lead' discovery for antidiarrhoeal drug development.
The Meliaceae family is well represented in Southern and Eastern Africa and Madagascar. Plants range in size from magnificent forest trees to small shrubs. Certain species are important as timber trees and they have wide-ranging uses in ethnomedicine in the region, prompting extensive investigation. Twenty-two of the fifty-one genera of the Meliaceae occur in the geographic area under review, and, of these, the chemistry of forty-four species, from nineteen genera, has been investigated. Compounds isolated include limonoids, mono-, di-, sesqui-, and triterpenoids, coumarins, chromones, lignans, flavonoids and other phenolics.Relatively few of the compounds and extracts from these species have been screened for biological activity, probably due to the limited screening facilities available in the area. However, properties including cytotoxicity against tumour cell lines, insect anti-feedant and anti-malarial activity, and uterotonic activity suggest that further extensive biological screening of compounds from this family is warranted.The similar chemistry of the genera Ptaeroxylon and Cedrelopsis support their grouping together in the distinct family Ptaeroxylaceae. Examination of the chemistry of species from this family suggests a close relationship with the Cneoraceae family.
Limonoids are the most distinctive secondary metabolites of the plant order Rutales. Recent work has established a wide range of biological activities for these compounds, including insect antifeedant and growth regulating properties, a variety of medicinal effects in animals and humans, and antifungal, bacteriocidal, and antiviral activity. This review summarizes the literature on the biological activities of limonoids of known structure, and attempts to relate those activities to current concepts of the evolution of the limonoids.
The seeds of Owenia acidula of Owenia venosa were found to contain a simple limonoid and a derivative of the cyclopropane protolimonoid glabretal, which has also been found in the timber of Aglaia ferruginea. The timber of Toona australis was found to contain cedrelone, and the timber seed of Xylocarpus moluccensis (sensu Mabberley) have been found to contain a rich mixture of limonoids. The chemotaxonomic significance of these results is discussed.
The fruit of Swietenia macrophylla is commonly known as “sky fruit”. The fruit, which contains flavonoids and saponins, is processed commercially into a wide range of health foods and healthcare products. The fruit concentrate is used traditionally to improve blood circulation and impart a healthy skin. In this paper, we describe the isolation and structure elucidation of three new phragmalin ortho esters, named swietephragmin H-J (1–3), and a new polyhydroxylated phragmalin, named swietemacrophine (4), from the leaves of S. macrophylla. The structures of the compounds were elucidated by spectroscopic methods, including HRESIMS, 1H NMR, 13C NMR, DEPT, 1H–1H COSY, HMQC, HMBC and NOESY spectra. This is the first report of phragmalin ortho esters and a polyhydroxylated phragmalin from this plant.
Chemical examination of the fruits of the Chinese mangrove plant, Xylocarpus granatum, resulted in the isolation and characterization of nine new limonoids, named xylocarpins A-I (1-5, 7-10), along with nine known limonoids. Xylocarpins A-E were designated as polyoxyphragmalins, xylocarpin I was identified as a phragmalin orthoester, while xylocarpins F-H represented mexicanolides modified by ring oxidation and unusual 9,10-bond cleavage. The structure of xyloccensin U was revised to be 6-dehydroxyxylocarpin D on the basis of 2D spectroscopic data.
Seven new phragmalins with a C-30 carbonyl moiety, named moluccensins A-G (1-7), among which moluccensins A-F, possessing a Delta(8,14) double bond, and moluccensin G (7), containing conjugated Delta(8,9) and Delta(14,15) double bonds, were isolated from the seeds of an Indian mangrove, Xylocarpus moluccensis. The structures of these compounds were established on the basis of single-crystal X-ray diffraction analysis and spectroscopic data. This is the first report of phragmalins with a conjugated C-30 carbonyl group.
Three new 16-norphragmalin limonoids, chukvelutins A-C (1-3), were isolated from the stem bark of Chukrasia tabularis var. velutina, which possess unprecedented skeletons, featured with a characteristic ketal moiety between the phragmalin skeleton and a biosynthetically extended isobutyryl group at C-15. Their structures were elucidated by extensive spectroscopic technologies.
A review of all naturally occurring plant orthoesters with various bioactivities that were discovered between 1960-2008 is presented. The review revealed the occurrence and distribution of plant orthoesters of daphnane diterpenoids, phragmalin limonoids, bufadienolide, and ergostane steroids. The review also focused on the structure activity relationship (SAR) or the mode-of-action of the biologically active orthoesters. It also discussed the approaches that were adopted to the orthoester subunit and synthetic efforts toward some of the biologically significant plant orthoesters. It was revealed that the presence of these orthoesters was limited to a few species and they were present mainly in the compound classes of daphnane diterpenoids, phragmalin limonoids, bufadienolide, and ergostane steroids.
The article deals with the chemical constituents isolated from all the Indian species of Xylocarpus viz. X. granatum, X. moluccensis, and X. mekongensis. A total of about 70 pure compounds of different classes have been covered. The article describes the biosynthetic pathway of limonoids and sources, bioactivities and chemical and physical constants of the different classes of compounds.
Four new limonoid derivatives, 1-O-methylichangensin (1), sudachinoid A (2), B (3), and C (4) were isolated from the seeds of Citrus sudachi, together with the known compounds ichangensin, obacunone, obacunoic acid and limonin, and the structures of the new compounds were elucidated based on spectroscopic and chemical evidence.
Two unique 8,9,30-phragmalin ortho esters, xyloccensins O (1) and P (2), were isolated from the mangrove plant Xylocarpus granatum. They are a new type of ortho ester of phragmalin. The structures were determined by spectroscopic and single-crystal X-ray diffraction techniques. The biogenetic pathway to these new phragmalins was also proposed. [structure: see text]
Five new phragmalin-type limonoids, xyloccensins Q-U (1-5), along with xyloccensin P were isolated from the stem bark of the mangrove plant Xylocarpus granatum. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as IR and MS spectroscopic data analyses.
The search for limonoids started long back when scientists started looking for the factor responsible for bitterness in citrus which has negative impact on citrus fruit and juice industry worldwide. The term limonoids was derived from limonin, the first tetranortriterpenoid obtained from citrus bitter principles. Compounds belonging to this group have exhibited a range of biological activities like insecticidal, insect antifeedant and growth regulating activity on insects as well as antibacterial, antifungal, antimalarial, anticancer, antiviral and a number of other pharmacological activities on humans. Although hundreds of limonoids have been isolated from various plants but, their occurrence in the plant kingdom is confined to only plant families of order Rutales and that too more abundantly in Meliaceae and Rutaceae, and less frequently in Cneoraceae and Harrisonia sp. of Simaroubaceae. Limonoids are highly oxygenated, modified terpenoids with a prototypical structure either containing or derived from a precursor with a 4,4,8-trimethyl-17-furanylsteroid skeleton. All naturally occurring citrus limonoids contain a furan ring attached to the D-ring, at C-17, as well as oxygen containing functional groups at C-3, C-4, C-7, C-16 and C-17. The structural variations of limonoids found in Rutaceae are less than in Meliaceae and are generally limited to the modification of A and B rings, the limonoids of Meliaceae are more complex with very high degree of oxidation and rearrangement exhibited in the parent limonoid structure. To counter the problem of bitterness in citrus juice and products genetic engineering of citrus to maximize the formation of limonoid glucosides for reducing limonoid bitterness is the focus of recent and future research. Regarding the biological activities of limonoids the investigations are to be directed towards detailed characterization, quantification, and designing a simple as well as versatile synthetic route of apparently important limonoids. Extraction methods too should be optimized; evaluation and establishment of pharmaco-dynamic and kinetic principles, and structure activity relationships should be a key goal associated with limonoids so that they can be safely introduced in our arsenal of pharmaceuticals to safeguard the humanity from the wrath of disease and its discomfort.
Three new polyhydroxylated phragmalins, named xyloccensins Y, Z(1), and Z(2) (1-3), were isolated from the fruit of a Chinese mangrove, Xylocarpus granatum, together with eight known compounds. The structures of these compounds were established on the basis of spectroscopic data and chemical methods.
The methanolic extracts of the barks and pneumatophores of Xylocarpus moluccensis were assessed for their effects on the central nervous system (CNS) using a series of established pharmacological tests including pentobarbitone-induced sleeping time, open field, hole cross, hole-board and evasions tests in mice model. These extracts produced a dose-dependent reduction of the onset and duration of pentobarbitone-induced hypnosis, reduction of locomotor and exploratory activities in the open field, hole cross, head-dip and evasion tests. These results suggest that both the bark and pneumatophore extracts possess CNS depressant activity, the pneumatophore extract being more potent than the bark extract.