Acrotrione B, a Prenylated and Highly Oxidized Xanthenoid with Antibacterial and Anti-proliferative Activities from the Roots of Acronychia pedunculata.

A new prenylated xanthenoid with a highly oxidized core, acrotrione B (1: ), together with six previously reported acetophenones (2:  - 7: ), were isolated from the roots of Acronychia pedunculata. The structures of the isolated compounds were elucidated by thorough analysis of their 1D and 2D NMR spectroscopic data. The relative and absolute configurations of acrotrione B were determined by electronic circular dichroism (ECD) calculations. Acrotrione B is an unusual, oxidized xanthenoid with a cyclohexadienone core that has not been previously reported. It thus represents a new skeletal type within the xanthenoid class. Acrotrione B (1: ) exhibited anti-proliferative activity against Hela (IC50 = 16.0 µM) and A549 (IC50 = 16.3 µM) cell lines. 5'-Prenylacrovestone (4: ) and acrovestone (5: ) were even more potent with IC50 values of 5.1 µM and 0.77 µM, respectively, against Hela cells and 11.8 µM and 1.13 µM, respectively, against A549 cells. Moreover, acrotrione B (1: ) displayed moderate antibacterial activities against Staphylococcus aureus, Bacillus cereus, and Bacillus subtilis, with MIC values in the range of 16 - 64 µg/mL. Finally, acropyrone (6: ) showed a significant suppression of lipopolysaccharide (LPS) induced NO production in murine macrophage J774.A1 cells (IC50 = 8.9 µM).

Bioactive xanthones, benzophenones and biphenyls from mangosteen root with potential anti-migration against hepatocellular carcinoma cells.

Liver cancer refers primarily to hepatocellular carcinoma (HCC) accounting for over 90% of cases and is the highest incidence in men in Thailand. Over the past decades, the incidence of HCC dramatically increased with a strong rise of mortality rates. Garcinia mangostana, "Queen of Fruit" of Thailand, is known as a rich source of xanthones with potent cytotoxic properties against various cancer cells. Study on xanthones is provoking not only due to the structural diversity but also a wide variety of pharmacological activities. Hence the aim of the current study is to determine the effects of metabolites from G. mangostana root on cell proliferation and migration of hepatocellular carcinoma cells. Twenty-two metabolites, including two new benzophenones and one new biphenyl, were isolated and characterized. Five xanthones with a prenyl moiety showed significant cytotoxicity against both HCC cells tested; however, only dulxanthone D displayed the most promising activity on the migration of Huh7 HCC cells, comparable to sorafenib, a standard drug. Moreover, the compound dose-dependently induced apoptosis in Huh7 cells via mitochondrial pathway. Accordingly, dulxanthone D held a great potential for development as a novel migration inhibitor for effective HCC treatment.

Picrotoxane sesquiterpene and α-pyrone derivative from Dendrobium signatum and their free radical scavenging potency.

One new picrotoxane sesquiterpene (1) and one new α-pyrone derivative (4), together with nine known compounds, were isolated from the aerial parts of Dendrobium signatum. The structures of the new compounds were elucidated based on the interpretation of 1D and 2D NMR, HRESIMS and electronic circular dichroism (ECD) data. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction data. The new α-pyrone 4 exhibited promising ABTS scavenging activity with IC50 value of 0.7 µM.

Two new xanthones from the root of Thai Calophyllum inophyllum and their toxicity against colon and liver cancer cells.

Two new xanthones, 1,3,6,7-tetrahydroxy-5-methoxy-4-(1',1'-dimethyl-2'-propenyl)-8-(3″,3″-dimethyl-2″-propenyl)-xanthone (1) and (2'S)-7-hydroxy caloxanthone B (2), were isolated from the root of Thai Calophyllum inophyllum Linn., together with twelve known xanthones (3-14). The structures of new compounds were elucidated based on spectroscopic data. In addition, compounds 4, 6 and 8 were isolated from the genus Calophyllum for the first time. The isolated compounds were evaluated for their cytotoxic activity against colon HCT-116 and liver Hep-G2 cancer cells. Among tested compounds, xanthones 5 and 14 possessing a prenyl moiety and a pyranyl ring fused at C-2 and C-3 displayed the most potent and selective cytotoxicity against HCT-116 colon cancers with the same IC50 values of 3.04 µM.

Two new rearranged clerodane diterpenes from Thai Tinospora baenzigeri.

A new rearranged clerodane-type diterpene (1), tinobaenzigeride, and a new rearranged clerodane glucoside (2) were isolated from the stems of Tinospora baenzigeri, along with four known compounds (3‒6). Their structures were elucidated by spectroscopic data analysis. In addition, the structure and configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 1 are a rare example of rearranged clerodanes, since it contains a fully oxygenated tetrahydrofuran moiety. The isolated compounds were evaluated for their cytotoxicity against Hep-G2 and MCF-7 cancer cells, none of them did show any significant activity at 25 µM.

Anti-Angiogenic Activity of Rotenoids from the Stems of Derris trifoliata.

The plants in the genus Derris have proven to be a rich source of rotenoids, of which cytotoxic effect against cancer cells seem to be pronounced. However, their effect on angiogenesis playing a crucial role in both cancer growth and metastasis has been seldom investigated. This study aimed at investigating the effect of the eight rotenoids (1: -8: ) isolated from Derris trifoliata stems on three cancer cells and angiogenesis. Among them, 12a-hydroxyrotenone (2: ) exhibited potent inhibition on both cell growth and migration of HCT116 colon cancer cells. Further, anti-angiogenic assay in an ex vivo model was carried out to determine the effect of the isolated rotenoids on angiogenesis. Results revealed that 12a-hydroxyrotenone (2: ) displayed the most potent suppression of microvessel sprouting. The in vitro assay on human umbilical vein endothelial cells was performed to determine whether compound 2: elicits anti-angiogenic effect and its effect was found to occur via suppression of endothelial cells proliferation and tube formation, but not endothelial cells migration. This study provides the first evidence that compound 2: could potently inhibit HCT116 cancer migration and anti-angiogenic activity, demonstrating that 2: might be a potential agent or a lead compound for cancer therapy.

Inhibition of TNF-α-Induced Inflammation by Sesquiterpene Lactones from Saussurea lappa and Semi-Synthetic Analogues.

We investigated the tumor necrosis factor-alpha (TNF-α) inhibitory activity of sesquiterpenes from Saussurea lappa root extracts. According to the hexane and EtOAc extracts showing significant activity with IC50 values of 0.5 and 1.0 µg/mL, respectively, chromatographic fractionation of the extracts was performed and led to the isolation of 10 sesquiterpenes (1: -10: ). Costunolide (1: ), a major compound, and dehydrocostus lactone (4: ) exhibited high efficiency in decreasing TNF-α levels, with IC50 values of 2.05 and 2.06 µM, respectively. In addition, sesquiterpene analogues were synthesized to establish their structure-activity relationship (SAR) profile. Among the semi-synthetic analogues, compounds 6A: and 16: showed the most potent activity with IC50 values of 1.84 and 1.97 µM, respectively. More importantly, compound 6A: showed less toxicity than costunolide and 16: . These results provided the first SAR profile of sesquiterpene lactones and indicated that the α-methylene-γ-lactone moiety plays a crucial role in TNF-α inhibition. Additionally, the epoxide derivative 6A: might represent a lead compound for further anti-TNF-α therapies, owing to its potent activity and reduced toxicity.

Suppression of inducible nitric oxide synthase pathway by 7-deacetylgedunin, a limonoid from Xylocarpus sp.

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.

Inhibitory effects of flavonoids from stem bark of Derris indica on the formation of advanced glycation end products.

ETHNOPHARMACOLOGICAL RELEVANCE: Derris indica (Lamk.) Bennet has been used in traditional medicine in many countries for the treatment of bronchitis, whooping cough, rheumatic joints and dipsia in diabetes. In addition, several studies have revealed that this plant displayed various pharmacological activities including anti-diabetic. The present study was designed to isolate the active compounds from its stem bark and evaluate their inhibitory activity on the formation of advanced glycation end products. MATERIAL AND METHODS: The EtOAc extract of the stem bark of Derris indica was isolated by column chromatographic techniques. The structures of isolated compounds were established on the basis of extensive spectroscopic methods. All compounds were assayed for their inhibitory effects on advanced glycation end products formation using BSA-methylglyoxal assay. RESULTS: Chromatographic fractionation of the EtOAc extract of Derris indica stem bark led to the isolation of two new pyranoflavonoids, derrisins A and B (1-2), along with 11 known flavonoids (3-13). The inhibitory activities of the compounds on the formation of advanced glycation end products were evaluated. Derrisin B (2) was the most active compound with IC50 value of 18.0µM, and displayed stronger inhibitory activity compared with positive control aminoguanidine. CONCLUSIONS: This study provided the possibility that a pyranoflavonoid (2) found in Derris indica might have therapeutic potential as an inhibitor against the formation of advanced glycation end products.

Antiangiogenetic effects of anthranoids from Alternaria sp., an endophytic fungus in a Thai medicinal plant Erythrina variegata.

Endophytic fungi are known as a prolific source for the discovery of structurally interesting and biologically active secondary metabolites, some of which are promising candidates for drug development. In the present study, three anthranoids were isolated from an Alternaria sp. endophytic fungus and evaluated for their antiangiogenic activity in a rat aortic sprouting assay, an ex vivo model of angiogenesis. Of these three compounds, altersolanol (2) was further characterized and found to show a promising activity in ex vivo, in vitro and in vivo angiogenesis asssays. Using human umbilical vein endothelial cells as an in vitro model, the angiogenic effect of 2 was found to occur via suppression of all three main functions of endothelial cells, namely proliferation, tube formation and migration.

Cytotoxic and anti-angiogenic properties of minor 3,4-seco-cycloartanes from Gardenia sootepensis exudate.

Gardenia plants have long been used as traditional medicines in various countries including Thailand. In this study, two new 3,4-seco-cycloartane triterpenes, sootependial (1) and sootepenoic acid (2), were isolated from bud exudate of G. sootepensis, together with five known compounds. Their structures were elucidated on the basis of spectroscopic data. Sootependial (1) showed potent cytotoxicity selective to Hep-G2 cell lines and anti-angiogenic activity in ex vivo model (a rat aortic ring sprouting) assay. Furthermore, its angiogenic effect was found to occur mainly by suppressing endothelial cell proliferation and tubule formation, suggesting the potential of 1 as a lead compound for cancer treatment.

Antiangiogenic activity of 3,4-seco-cycloartane triterpenes from Thai Gardenia spp. and their semi-synthetic analogs.

Twelve naturally occurring 3,4-seco-cycloartane triterpenes (1-12) isolated from Gardenia sootepensis and Gardenia obtusifolia, and eight semi-synthetic derivatives (13-20) were evaluated for their antiangiogenic activity on a rat aortic sprouting assay, an ex vivo model of angiogenesis. Among these compounds, sootepin B (1) displayed the most potent activity in terms of the inhibition of microvessel sprouting from rat aortic rings in a dose-dependent manner with IC(50) value of 4.46 µM. Its angiogenic effect was found to occur via suppression of endothelial cell proliferation and tubular formation, and was likely mediated by regulation (inhibition) of the Erk1/2 signaling pathway.

Cytotoxic 3,4-seco-cycloartane triterpenes from Gardenia sootepensis.

Five new 3,4-seco-cycloartanes, sootepins A-E (1-5), along with four known triterpenes (6-9), were isolated from the apical buds of Gardenia sootepensis. Their structures were elucidated on the basis of spectroscopic methods (1D and 2D NMR, HRESIMS, and X-ray crystallography), and the compounds were tested for in vitro cytotoxic activity against human breast (BT474), lung (CHAGO), liver (Hep-G2), gastric (KATO-3), and colon (SW-620) cancer cell lines. Generally, the compounds possessing an exomethylene gamma-lactone ring showed broad cytotoxicity for all cell lines tested.

Cassane furanoditerpenoids from the seed kernels of Caesalpinia bonduc from Thailand.

Three new cassane furanoditerpenoids ( 1- 3), together with 13 known cassane diterpenes ( 4- 16), were isolated from the EtOAc extract of the seed kernels of Caesalpinia bonduc. Their structures were elucidated on the basis of spectroscopic analysis, mainly NMR and MS. Compounds 1- 3 exhibited good antimalarial activity against the multidrug-resistant K1 strain of Plasmodium falciparum, while compound 4 was inactive. None of the compounds were cytotoxic against any of the tumor cell lines tested.

Furanocembranoids from the stem bark of Croton oblongifolius.

Four novel furanocembranoids (1-4) were isolated from the stem bark of Croton oblongifolius. Their structures were elucidated on the basis of spectroscopic analysis, mainly NMR and MS. Compounds 1, 3, and 4 exhibited good cytotoxicity against several human tumor cell lines.

Cytotoxic constituents from Butea superba Roxb.

A carpin (3-hydroxy-9-methoxypterocarpan) (Medicarpin) (1) and four isoflavones, 7-hydroxy-4'-methoxy-isoflavone (Formononetin) (2); 7,4'-dimethoxyisoflavone (3); 5,4'-dihydroxy-7-methoxy-isoflavone (Prunetin) (4) and 7-hydroxy-6,4'-dimethoxyisoflavone (5) were isolated from the tuber roots of Butea superba Roxb. Compounds 2 and 4 showed moderate cytotoxic activity on KB cell lines with IC(50) (microM) values of 37.3+/-2.5 and 71.1+/-0.8 and on BC cell lines with IC(50) (microM) values of 32.7+/-1.5 and 47.3+/-0.3, respectively.