Vilailak Prachyawarakorn

Hybrid flavan-chalcones, aromatase and lipoxygenase inhibitors, from Desmos cochinchinensis

Hybrid flavan-chalcones, desmosflavans A (1) and B (2), together with three known compounds, cardamonin (3), pinocembrin (4) and chrysin (5), were isolated from leaves of Desmos cochinchinensis. Cardamonin (3) and chrysin (5) exhibited potent antioxidant activity with 15.0 and 12.2 ORAC units. Desmosflavans A (1) and B (2), pinocembrin (4), and chrysin (5) were found to be inhibitors of aromatase with respective IC50 values of 1.8, 3.3, 0.9, and 0.8 μM. Desmosflavan A (1) inhibited lipoxygenase with the IC50 value of 4.4 μM. Desmosflavan A (1) exhibited cytotoxic activity with IC50 values of 0.29-3.75 μg/mL, while desmosflavan B (2) showed IC50 values of 1.71-27.0 μg/mL.

Cytotoxic sesquiterpenes from the endophytic fungus Pseudolagarobasidium acaciicola.

Twenty previously unknown compounds and two known metabolites, merulin A and merulin D, were isolated from the endophytic fungus Pseudolagarobasidium acaciicola, which was isolated from a mangrove tree, Bruguiera gymnorrhiza. Structures of the 20 compounds were elucidated by analysis of spectroscopic data. The absolute configuration of seven of these compounds was addressed by a single crystal X-ray analysis using CuKα radiation and an estimate of the Flack parameter. Three compounds also possessed a tricyclic ring system. Terpene endoperoxides isolated exhibited cytotoxic activity, while those without an endoperoxide moiety did not show activity. The endoperoxide moiety of sesquiterpenes has significant impact on cytotoxic activity, and thus is an important functionality for cytotoxicity. One terpene endoperoxide displayed potent cytotoxic activity (IC50 0.28μM), and selectively exhibited activity against the HL-60 cell line.

Investigation of some bioactive Thai medicinal plants

It has been estimated that plants are the most important source of medicine for more than 80% of the world’s population. Medicinal plants are a vital source of medication in developing countries. Despite the wealth of human experience and folklore concerning the medicinal uses of plants, proper scientific investigation has only been applied to a small fraction of the world’s plants. This is a cause of grave concern as plant species continue to disappear. A rapid response to this situation is urgently needed to prevent the disappearance of the plant species and the ethnopharmacological knowledge that accompanies them. In this review, recent work on the investigation of selected bioactive Thai medicinal plants is presented. Their biological activities against infectious diseases including antimalarial and anti-HIV, are highlighted, as well as their anticancer, antiulcer and anti-inflammatory properties. The chemical transformations of some selected compounds are discussed.

Cytotoxic metabolites from the endophytic fungus Penicillium chermesinum: discovery of a cysteine-targeted Michael acceptor as a pharmacophore for fragment-based drug discovery, bioconjugation and click reactions

Fungal metabolites (1–8) including known compounds, TMC-264 (1), PR-toxin (6) and a sesquiterpene (7), and new natural products 2–5 and 8, were isolated from the mangrove endophytic fungus Penicillium chermesinum. Compound 2 was a novel tetracyclic polyketide uniquely spiro-attached with a γ-lactone ring. Compounds 1 and 6 exhibited comparable cytotoxic activity to that of doxorubicin, and they selectively exhibited activity toward certain cancer cell lines. The cytotoxicity of 1 might be due to the β-chloro substituted α,β-unsaturated ketone functionality, which was reactive toward glutathione and peptides containing a thiol group. The polyketide 1 reacted with glutathione and peptides under physiological conditions, and its thiol-reactive pharmacophore is possibly applicable to the design of glutathione modulation agents, fragment-based drug discovery (for irreversible enzyme inhibitors), bioconjugation, and click reactions. Facile C–S bond formation in water (catalyst-free conditions) inspired by 1 could also be useful for green chemistry.

NMR study of seven coumarins from Mammea siamensis

Seven known mammea coumarins, mammea A/AA cyclo D ( 1 ), mammea A/AD cyclo D ( 2 ), mammea A/AB cyclo D ( 3 ), mammea A/AC cyclo F ( 4 ), mam-mea A/AB cyclo F ( 5 ), mammea A/AA cyclo F ( 6 ), mammea B/AC cyclo F ( 7 ), were isolated for the first time from the hexane extract of Mammea siamensis . A detailed analysis of both 1D and 2D NMR spectral data of these compounds was made.

Glutarimide Alkaloids and a Terpenoid Benzoquinone from Cordia globifera

Three new compounds, a meroterpene (2) having a cyclopropane moiety named globiferane and glutarimide alkaloids named cordiarimides A (3) and B (4), were isolated from the roots of Cordia globifera. Compounds 2-4 exhibited weak cytotoxic activity. Cordiarimide B (4) exhibited radical scavenging activity, as it inhibited superoxide anion radical formation in the xanthine/xanthine oxidase (XXO) assay, and also suppressed superoxide anion generation in differentiated HL-60 human promyelocytic leukemia cells when induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). This is the first report on the presence of glutarimide alkaloids in the genus Cordia.

Terpenoids from the roots of Drypetes hoaensis and their cytotoxic activities.

Seven terpenoids consisting of five sesquiterpenoids, hoaensieremone, hoaensieremodione, hoaensifuranonal, hoaensieudesone, and hoaensibenzofuranal, and two friedelane triterpenoids, 3α-(E)-p-coumaroyloxyfriedelan-7-one and 3α-(E)-caffeoyloxyfriedelan-7-one were isolated from the dichloromethane extract of the roots of Drypetes hoaensis. Additionally, twelve known compounds and vanillin were isolated. Their structures were established on the basis of spectroscopic analysis, as well as by comparison with literature data. The anticancer activity of nine of these compounds was investigated.

Flavans from Desmos cochinchinensis as potent aromatase inhibitors

Flavans from the roots of Desmos cochinchinensis exhibited potent aromatase inhibitory activity at nanomolar levels, and could be leads for the development of anti-aromatase drugs. In addition, these aromatase inhibitors did not show pronounced cytotoxic activity. Flavans exert their inhibitory activity through binding, as revealed by molecular docking studies, with aromatase at Arg115, Met374, and Leu477; the C-7 hydroxyl (or methoxyl) forms hydrogen bonds with Met374 and Arg115 of aromatase.

Bioactive cardinane sesquiterpenes from the stems of Alangium salviifolium.

A dichloromethane extract of the stems of Alangium salviifolium afforded twelve cardinane sesquiterpenes, seven of which are new alangenes A-G (1-7) and five known compounds (8-12). Their structures were elucidated on the basis of spectroscopic techniques including UV, IR, and NMR spectroscopies, and mass spectrometry. Most of the tested compounds exhibited very potent aromatase inhibition properties, especially in the case of the cardinane sesquiterpenes 1, 5-8, and 10 (IC50 values of 0.09, 0.13, 0.30, 0.06, 2.05, and 1.19 μM, respectively), which are significantly better than that of the positive control (ketoconazole, IC50 of 2.4 μM). Compounds 1 and 4 exhibited selective cytotoxicity against the MOLT-3 cancer cell line with IC50 values of 7.9 and 2.1 μg mL(-1) , respectively.

5-formylfurfuryl esters from Duabanga grandiflora.

5-Formylfurfuryl esters, duabanganals A-D, together with sixteen known compounds, a known 5-formylfurfuryl ester, latifolinal, eight pentacyclic triterpenes, a benzofuran derivative, an ellagic acid derivative, vanillin, β-sitosterol, β-sitosterol glucoside, 3-hydroxy-4-methoxycinnamaldehyde, and 5-formylfurfurol, were isolated from the stem bark of Duabanga grandiflora. The structures of these compounds were elucidated on the basis of spectroscopic analysis. Several of these metabolites were evaluated for cytotoxic activities against six cancer cell lines.