Study on the absolute configuration and biological activity of rotenoids from the leaves and twigs of Millettia pyrrhocarpa Mattapha, Forest & Hawkins, sp. Nov.

BACKGROUND: M. pyrrhocarpa is a new plant in the Fabaceae: Faboideae family that is found in Thailand. A literature search revealed that the Milletia genus is rich in bioactive compounds possessing a wide range of biological activities. In this study, we aimed to isolate novel bioactive compounds and to study their bioactivities. METHODS: The hexane, ethyl acetate, and methanol extracts from the leaves and twigs of M. pyrrhocarpa were isolated and purified using chromatography techniques. These extracts and pure compounds were tested in vitro for their inhibitory activities against nine strains of bacteria, as well as their anti-HIV-1 virus activity and cytotoxicity against eight cancer cell lines. RESULTS: Three rotenoids, named 6aS, 12aS, 12S-elliptinol (1), 6aS, 12aS, 12S-munduserol (2), dehydromunduserone (3), and crude extracts were evaluated for antibacterial, anti-HIV, and cytotoxic activities. It was found that compounds 1-3 inhibited the growth of nine strains of bacteria, and the best MIC/MBC values were obtained at 3/ > 3 mg/mL. The hexane extract showed anti-HIV-1 RT with the highest %inhibition at 81.27 at 200 mg/mL, while 6aS, 12aS, 12S-elliptinol (1) reduced syncytium formation in 1A2 cells with a maximum EC50 value of 4.48 µM. Furthermore, 6aS, 12aS, 12S-elliptinol (1) showed cytotoxicity against A549 and Hep G2 cells with maximum ED50 values of 2.27 and 3.94 µg/mL. CONCLUSION: This study led to the isolation of constituents with potential for medicinal application, providing compounds (1-3) as lead compounds against nine strains of bacteria. The hexane extract showed the highest %inhibition of HIV-1 virus, Compound 1 showed the best EC50 in reducing syncytium formation in 1A2 cells, and it also showed the best ED50 against human lung adenocarcinoma (A549) and human hepatocellular carcinoma (Hep G2). The isolated compounds from M. pyrrhocarpa offered significant potential for future medicinal application studies.

Bioactive tetrahydrofuran lignans from roots, stems, leaves and twigs of Anogeissus rivularis.

Four previously undescribed tetrahydrofuran lignans, named anorisols A-D (1-4) and fourteen known compounds (5-18) were isolated from the roots, stems, leaves and twigs of Anogeissus rivularis. The chemical structures were elucidated on the basis of their spectroscopic data and by comparison with the literature data. The absolute configurations of 1-4 were established by comparison of the experimental ECD spectra with the calculated ECD spectra. Some isolated compounds were evaluated for their cytotoxic activity as well as anti-HIV-1 activity employing reverse transcriptase (RT) and syncytium reduction assays using the ΔTat/RevMC99 virus in 1A2 cell line systems. Compound 6 displayed the most potent activity in syncytium inhibition assay with effective concentration at 50% (EC50) value of 13.3 µM (SI >3.0). In the reverse transcriptase assay, compound 1 exhibited moderate activity with IC50 value of 213.9 µM.

Boesenmaxane Diterpenoids from Boesenbergia maxwellii.

Three new diterpenoids, boesenmaxanes A-C (1-3), with an unprecedented core skeleton consisting of an unusual C-C bond between C-12 and an exo-cyclic methylene C-13, were isolated from the rhizome extracts of Boesenbergia maxwellii. The structures were elucidated by analysis of spectroscopic and X-ray diffraction data. Electronic circular dichroism spectra were used to determine the absolute configuration. All the isolates were evaluated for their cytotoxic effects, anti-HIV activity, and antimicrobial activity. Boesenmaxanes A and C (1 and 3) showed significant inhibitory activity in the syncytium reduction assay, with EC50 values of 55.2 and 27.5 µM, respectively.

Cytotoxic compounds from the leaves and stems of the endemic Thai plant Mitrephora sirikitiae.

Context: Mitrephora sirikitiae Weeras., Chalermglin & R.M.K. Saunders (Annonaceae) is a plant endemic to Thailand. Its constituents and their biological activities are unknown.Objective: Isolation and identification of the compounds in the leaves and stems of M. sirikitiae and determination of their cytotoxicity.Materials and methods: Methanol extracts of the leaves and stems of M. sirikitiae were separated by chromatography, and spectroscopic methods were used to determine the structures of the components. The cytotoxicity of the extracts and pure compounds was evaluated using the sulforhodamine B assay with several cell lines. The cells were treated with the compounds at concentrations of 0.16-20 µg/mL for 48 or 72 h.Results: The investigation of the extracts of M. sirikitiae leaves and stems resulted in the isolation of a new lignan, mitrephoran, and 15 known compounds. Among these compounds, 2-(3,4-dimethoxyphenyl)-6-(3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, ciliaric acid, 6-methoxymarcanine A, and stepharanine were isolated from this genus for the first time. The alkaloids liriodenine and oxoputerine exhibited strong cytotoxicity against all tested cells (IC50 values of 6.59-11.02 µM). In contrast, magnone A, 3',4-O-dimethylcedrusin, and 6-methoxymarcanine A inhibited the growth of some of the tested cells (IC50 values of 2.03-19.73 µM). Magnone A and 6-methoxymarcanine A showed low toxicity for Hek 293 cells (IC50 >20 µM).Discussion and conclusions: M. sirikitiae is a source of cytotoxic lignans and alkaloids. Among the cytotoxic compounds, magnone A and 6-methoxymarcanine A are potentially useful lead compounds for the further development of anticancer agents because of their selective inhibitory effects on cancer cell lines.

Cytotoxic polyoxygenated cyclohexene derivatives from the aerial parts of Uvaria cherrevensis.

Three previously undescribed polyoxygenated cyclohexene derivatives named cherrevenol M (1), cherrevenol N (2), and cherrevenone (3), together with nine related known analogues 4-12 were isolated from the ethyl acetate fraction partitioned from the methanol extract of the aerial parts of Uvaria cherrevensis (Annonaceae). The determination of the structures and their relative configurations of the isolated compounds were established by spectroscopic techniques, electronic circular dichroism (ECD) analysis as well as comparison with the literature data. For cherrevenone (3), the relative and absolute configurations were also confirmed by using X-ray diffraction and ECD techniques, respectively. Compounds isolated except for compounds 8 and 10 were evaluated for their cytotoxic activity and cherrevenone (3) showed moderate cytotoxic activity against all cancerous cell lines except for ASK cell line with ED50 values ranging from 1.04 ±â€¯0.13 to 10.09 ±â€¯4.31 µM.

A New Neolignan, and the Cytotoxic and Anti-HIV-1 Activities of Constituents from the Roots of Dasymaschalon sootepense.

Bioassay-guided isolation from the ethyl acetate extract of Dasymaschalon sootepense roots led to the isolation of twelve compounds including a new dihydrobenzo-furan neolignan, (+)-(2S,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-methylbenzofuran-5-carbaldehyde (5), and eleven known compounds (1-4, and 6-12). The chemical structures and stereochemistry of all the isolated compounds were established by spectroscopic techniques. The known compounds 4 and 6 have been fully characterized spectroscopically, including their absolute configurations. Cytotoxic and anti-HIV-1 reverse transcriptase (RT) activities of compounds 1-3, 5 and 8-12 were determined. Among compounds screened, compounds 2, 3 and 10 displayed weak cytotoxic activity with ED50 values ranging from 9.6-47.5 µM and only compound 2 was found weakly active against HIV-1 RT with an IC50 value of 323.2 µM.

Polyoxygenated cyclohexene derivatives isolated from Dasymaschalon sootepense and their biological activities.

Six new naturally occurring polyoxygenated cyclohexene derivatives together with eight related known derivatives, two known alkaloids, and two known flavonoid derivatives were isolated from bioassay-guided fractionation of the ethyl acetate extract of the leaves and twigs of Dasymaschalon sootepense. The structure elucidation and determination of absolute configurations were established by various spectroscopic methods, X-ray diffraction techniques as well as comparison with the literature data. Several isolated compounds were evaluated for their cytotoxic, anti-HIV-1 RT and anti-inflammatory activities.

Cytotoxic alkaloids from leaves and twigs of Dasymaschalon sootepense.

Bioassay-guided fractionation of the cytotoxic ethyl acetate fraction of the sequential methanol extract from the leaves and twigs of Dasymaschalon sootepense led to the isolation of a new 7-hydroxy aporphine alkaloid, 6a,7-dehydrodasymachaline (1) along with the five known compounds (-)-nordicentrine (2), dicentrinone (3), (-)-sinactine (4), aristolactam AII (5) and epiberberine (6). Their structures were elucidated by spectroscopic methods. This is the first report of alkaloids 1-2 and 5-6 from the genus Dasymaschalon. Compounds 1 and 5 showed cytotoxicity against a panel of cancer cell lines.

Cytotoxic aporphine alkaloids from leaves and twigs of Pseuduvaria trimera (Craib).

From ethyl acetate-methanol extracts of leaves and twigs of Pseuduvaria trimera a new aporphine alkaloid; 8-hydroxy-1,4,5-trimethoxy-7-oxoaporphine or 8-hydroxyartabonatine C (1) was isolated, together with the known 1,2,3-trimethoxy-4,5-dioxo-6a,7-dehydroaporphine (ouregidione, 2). Their structures were elucidated by a combination of spectral methods; mainly 2D NMR; IR and MS. Compounds 1 and 2 exhibited cytotoxic activity with IC50 values of 26.36±5.18 µM and 12.88±2.49 µM, respectively, for human hepatocellular carcinoma HepG2 cells, and 64.75±4.45 and 67.06±3.5 µM, respectively, for human breast cancer MDA-MB231 cells. Both compounds displayed anti-cancer activity but less than that of doxorubicin; a conventional chemotherapeutic drug, the IC50 levels of which were 2.21±1.72 and 1.83±0.09 µM for HepG2 and MDA-MB231 cells, respectively.

Sawtehtetronenin from Goniothalamus sawtehii and its cytotoxicity.

A new acetogenin has been isolated from the ethyl acetate extract of leaves and twigs of G. sawtehii (Annonaceae). The structure of compound 1 was identified as sawtehtetronenin on the basis of spectral evidence (UV, IR, MS and 1H, and 13C NMR) and by comparison with related compounds. Sawtehtetronenin was found to be cytotoxic to human hepatocellular carcinoma HepG2 and breast cancer MDA-MB231 cells with IC50 values of 79.3 ± 11.9 µM and 108.1 ± 1.5 µM, respectively. Compound 1 was less toxic to both cell lines when compared with camptothecin, a chemotherapeutic drug.

Antiproliferative effect of alkaloids via cell cycle arrest from Pseuduvaria rugosa.

CONTEXT: Pseuduvaria rugosa (Blume) Merr. (Annonacaea) grows widely in the south and southeast regions of Thailand. Preliminary screening for biological activities revealed that crude hexane, ethyl acetate, and acetone extracts from mixtures of leaves and twigs of P. rugosa showed cytotoxicity. OBJECTIVE: Chemical constituents and their antiproliferative activity in K562, U937, and HL-60 human leukemic cell lines from P. rugosa were performed for the first time. MATERIALS AND METHODS: The isolated compounds were obtained from chromatographic separation. The structures were established by spectroscopic techniques including IR, UV, NMR together with 2D NMR (HMBC, COSY, and NOE) and MS. The K562, U937, and HL-60 cell lines were treated with isolated aporphine alkaloids (0-100 µg/mL) and cell viability was measured with the MTT assay. Cell cycle analysis was performed using propidium iodide (PI) based staining methods. RESULTS: Two known aporphine alkaloids, 1,2,3-trimethoxy-5-oxonoraporphine (1) and ouregidione (2) were isolated. Treatment of the cells with compounds 1 and 2 at a concentration of 100 µg/mL for 72 h reduced the viability of K562, U937, and HL-60 cell lines to 63 and 64, 38 and 66, and 49 and 64%, respectively. In addition, compounds 1 and 2, at a concentration of 100 µg/mL, exposed to U937 and HL-60 cell lines showed cell cycle arrest. The U937 cell line treated with compounds 1 and 2 increased significantly the proportion of the cell in S phase, whereas the HL-60 cell line-induced G2/M and G1 phase, respectively. DISCUSSION AND CONCLUSION: The results showed that 1,2,3-trimethoxy-5-oxonoraporphine and ouregidione-induced cytotoxicity with HL-60, U937, and K562 cells where 1,2,3-trimethoxy-5-oxonoraporphine was more active than ouregidione.

Aristolactam-type alkaloids from Orophea enterocarpa and their cytotoxicities.

A new aristolactam, named enterocarpam-III (10-amino-2,3,4,6-tetramethoxy phenanthrene-1-carboxylic acid lactam, 1) together with the known alkaloid stigmalactam (2), were isolated from Orophea enterocarpa. Their structures were elucidated on the basis of interpretation of their spectroscopic data. Compounds 1 and 2 exhibited significant cytotoxicities against human colon adenocarcinoma (HCT15) cell line with IC(50) values of 1.68 and 1.32 µM, respectively.

New clerodane diterpenoid from the bulbils of Dioscorea bulbifera.

A new clerodane diterpenoid has been isolated from the acetone extract of bulbils of Dioscorea bulbifera. The structure of compound 1 was established as 15,16-epoxy-6alpha-O-acety1-8beta-hydroxy- 9-nor-clero-13(16),14-diene-17,12;18,2-diolide on the basis of comprehensive spectroscopic techniques.

Cytotoxic alkaloids from stems, leaves and twigs of Dasymaschalon blumei.

Bioassay-guided fractionation of the cytotoxic ethyl acetate extract from the stems of Dasymaschalon blumei (Annonaceae) led to the isolation of four aristololactam alkaloids, including the hitherto unknown 3,5-dihydroxy-2,4-dimethoxyaristolactam (1), as well as the three known compounds, aristolactam BI, goniopedaline, and griffithinam. Additionally, the cytotoxic extract from the combined leaves and twigs of the same plant yielded three known oxoaporphine alkaloids, oxodiscoguattine, dicentrinone, and duguevalline. The structures of aristolactams and oxoaporphine alkaloids were elucidated on the basis of spectroscopic methods. All isolates were evaluated for cytotoxicity against a panel of mammalian cancer cell lines and a noncancerous human embryonic kidney cell Hek 293.

A new azafluorenone from the roots of Polyalthia cerasoides and its biological activity.

Chromatographic separation of the ethyl acetate extract of roots of Polyalthia cerasoides has led to the isolation of the new compound, 6,8-dihydroxy-7-methoxy-1-methyl-azafluorenone. This compound exhibited potent cytotoxic activities with IC50 values in the range of 2.64-3.58 microg x mL(-1) for A549, GLC4 and GLC4/Adr cells, but was not recognized by ABCC1/MRP1 protein. The compound also showed very strong inhibition of M. tuberculosis using a broth microdilution method, with an MIC value of 0.78 microg x mL(-1), which was equal to that of ofloxacin, one of the four antibiotic drugs used as a positive control.