Anti-androgenic effect of sesquiterpenes isolated from the rhizomes of Curcuma aeruginosa Roxb

Six sesquiterpenes: germacrone (1), zederone (2), dehydrocurdione (3), curcumenol (4), zedoarondiol (5) and isocurcumenol (6) were isolated from rhizomes of Curcuma aeruginosa Roxb. (Zingiberaceae). They inhibited 5α-reductase which converts testosterone to dihydrotestosterone (DHT). Germacrone (1) was the most potent (IC(50)=0.42±0.05 mg/mL). Compound 1 was anti-androgenic in LNCaP cells when proliferation was testosterone-induced. The growth of flank gland of male Syrian hamsters is dependent on circulating androgen and when maintained with testosterone, 1 (3, 30, 100μg) inhibited growth but was ineffective against DHT. The similar activity profile was observed on the 5α-reductase inhibitor, finasteride (100 μg) treatment group. The androgen receptor binding assay showed that 1 did not bind to the androgen receptor. In conclusion, 1 showed anti-androgenic effect on in vitro and in vivo assays. One of the possible mechanisms was inhibition 5α-reductase activity. Thus, 1 is a potential lead compound for treatment of androgen-dependent disorders.     

Cytotoxic triterpene saponins from the leaves of Aralia elata

Phytochemical investigation of the leaves of Aralia elata has led to the isolation of four new compounds, 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosyl (1→3)-β-D-glucopyranosyl oleanolic acid (1), 3-O-[β-D-glucopyranosyl (1→3)-β-D-glucopyranosyl (1→3)]-[β-D-glucopyranosyl (1→2)]-β-d-glucopyranosyl hederagenin 28-O-β-D-glucopyranoside (2), 3-O-{[β-D-glucopyranosyl (1→2)]-[β-d-glucopyranosyl (1→3)-β-d-glucopyranosyl (1→3)]-β-D-glucopyranosyl} oleanolic acid 28-O-β-D-glucopyranosyl ester (3) and 3-O-[β-D-glucopyranosyl (1→2)]-[β-D-glucopyranosyl (1→3)]-β-d-glucopyranosyl caulophyllogenin (4) and two known compounds, 3-O-[β-D-glucopyranosyl (1→3)-α-l-arabinopyranosyl]-echinocystic acid (5) and 3-O-α-L-arabinopyranosyl echinocystic acid (6). The structural determination was accomplished with spectroscopic analysis, in particular (13)C-NMR, 2D-NMR and HR-ESI-MS techniques. Compounds 1-6 were tested for their inhibition of the growth of HL60, A549 and DU145 cancer cells. Compound 1 showed significant cytotoxic activity against HL60 and A549 cancer cells with IC(50) values of 6.99μM and 7.93μM respectively. In addition, compounds 5 and 6 showed significant cytotoxic activity against HL60 cancer cells with IC(50) values of 5.75μM and 7.51μM, respectively.     

A cytotoxic 4α-methyl steroid from the aerial parts of Cimicifuga foetida L

A new 4α-methyl sterol, cimisterol A (1), together with five known compounds (2-6), were isolated from the aerial parts of Cimicifuga foetida L. The new compound's structure was determined with the help of extensive 1D and 2D NMR spectroscopy. Compound 1 exhibited broad-spectrum and potent cytotoxic activities against human HL-60, Jurkat, K562, U937, HepG-2, and SGC-7091 cell lines, with IC(50) values of 7.23, 2.89, 6.88, 3.38, 4.21, and 4.89 μM, respectively. Compound 3 showed moderate to weak activities to all cell lines, except for SGC-7091, having IC(50) values ranging from 13.37 to 17.72 μM. This is the first time a cytotoxic 4α-methyl sterol constituent was discovered from Cimicifuga spp.     

Bioactivity-guided fractionation of the lipoxygenase and cyclooxygenase inhibiting constituents from Chisocheton polyandrus Merr

Lipoxygenase (LOX)-inhibiting compounds from the leaves of Chisocheton polyandrus Merr. were isolated in this study using a bioactivity-guided fractionation technique. Two dammarane triterpenoids, dammara-20,24-dien-3-one (1) (IC(50)=0.69±0.07 μM) and 24-hydroxydammara-20,25-dien-3-one (2) (IC(50)=1.11±0.38 μM), were isolated and identified based on the soybean LOX assay. Dammara-20,24-dien-3-one (1) exhibited dual inhibition of both human 5-LOX (IC(50)=24.27±2.92 μM) and cyclooxygenase-2 (COX-2) (IC(50)=3.17±0.90 μM), whereas 24-hydroxydammara-20,25-dien-3-one (2) did not exhibit any significant inhibitory effects. This report is the first to detail the inhibition of LOX and COX by both C. polyandrus and its isolated compounds.     

Flavonoids with antiplasmodial and cytotoxic activities of Macaranga triloba

A new flavanone derivative, malaysianone A (1), four prenylated flavanones, 6-prenyl-3'-methoxyeriodictyol (2), nymphaeol B (3), nymphaeol C (4) and 6-farnesyl-3',4',5,7-tetrahydroxyflavanone (5), and two coumarins, 5,7-dihydroxycoumarin (6) and scopoletin (7), were isolated from the dichloromethane extract of the inflorescences of Macaranga triloba. The structures of these compounds were elucidated based on spectroscopic methods including nuclear magnetic resonance (NMR-1D and 2D), UV, IR and mass spectrometry. The cytotoxic activity of the compounds was tested against several cell lines, with 5 inhibiting very strongly the growth of HeLa and HL-60 cells (IC(50): 1.3 μg/ml and 3.3 μg/ml, respectively). Compound 5 also showed strong antiplasmodial activity (IC(50): 0.06 μM).     

Bisindole alkaloids and secoiridoids from Alstonia macrophylla Wall. ex G. Don

The ethanolic extract from stems of a Thai medicinal plant, Alstonia macrophylla Wall. ex G. Don (Apocynaceae) showed a significant inhibitory effect on acetylcholinesterase (AChE) determined by using Ellman assay. Four compounds i.e., a bisindole alkaloid, macralstonine (1), a new bisindole alkaloid, thungfaine (2), a secoiridoid glycoside, sweroside (3) and a new secoiridoid glycoside, naresuanoside (4) were isolated. Compound 4 showed moderate AChE and butyrylcholinesterase (BChE) inhibitory effects. Interestingly, compound 4 inhibited cell growth on human androgen-sensitive prostate cancer cell line (LNCaP) but no effect on viability of human foreskin fibroblast cells (HF).     

Cytotoxic sesquiterpenoids from the fruits of Lindera communis

A new sesquiterpenoid, namely Linerenone (1), together with three known sesquiterpenoids (2–4), were isolated from the fruits of Lindera communis. Their structures were determined by extensive spectroscopic analysis including 1D, 2D-NMR and HR-MS spectra. Compound 1 showed significant cytotoxic activity against H460, ES2 and DU145 cancer cells with IC₅₀ of 2.1 μg/mL, 2.8 μg/mL and 3.0 μg/mL, respectively.     

Anti-neuroinflammatory constituents from Polygala tricornis Gagnep

Two new compounds (S)-(+)-butyl-4-methylene-5-oxo-pyrrolidin-2-carboxylate (1) and (5-formylfuran-2-yl)methyl 4-hydroxy-2-methylenebutanoate (2), together with four known compounds (3-6) were isolated from the roots of Polygala tricornis Gagnep. Their structures were determined on the basis of 1D- and 2D-NMR experiments and by comparison with physical data of known compounds. All the isolated compounds were examined for their inhibitory effect on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 microglial cells, and compounds 1 and 2 exhibited pronounced inhibition on the NO production with IC(50) values of 14.1 μM and 1.77 μM, respectively.     

Echinosporins as new cell cycle inhibitors and apoptosis inducers from marine-derived Streptomyces albogriseolus

Bioassay-guided fractionation of the ethyl acetate extract from the fermentation broth of marine-derived Streptomyces albogriseolus A2002 led to the isolation of echinosporin (1) and 7-deoxyechinosporin (2). Compound 1 inhibited the proliferation of tsFT210, K562 and HCT-15 cancer cells (IC(50) 91.5 microM, 25.1 microM and 247 microM respectively) and 2 showed the same effect on K562 cells (IC(50) 143 microM). Flow cytometric analysis suggested that 1 and 2 exert their anti-proliferative effects on those cells through inhibiting cell cycle at the G(2)/M phase and inducing apoptosis.     

Lignans from the heartwood of Streblus asper and their inhibiting activities to hepatitis B virus

Three new lignans, erythro-strebluslignanol (1), threo-7'-methoxyl strebluslignanol (2) and erythro-7'-methoxyl strebluslignanol (3), together with twelve known compounds were isolated from the n-butanol and chloroform fractions of the heartwood of Streblus asper. Their structures were elucidated through extensive spectroscopic methods, including MS and 2D NMR experiments (HMQC and HMBC). The stereochemistry at the chiral center was determined using CD spectra, as well as analysis of coupling constants and optical rotation data, respectively. Primary bioassays showed that 6-hydroxyl-7-methoxyl-coumarin (5) and ursolic acid (10) showed anti-HBV activities, with IC(50) values of 29.60 μM and 89.91 μM for HBsAg at no cytotoxicity, and IC(50) values of 46.41 μM and 97.61 μM for HBeAg at no cytotoxicity, respectively.     

Anti-inflammatory and cytotoxic 2-arylbenzofurans from Morus wittiorum

Three new 2-arylbenzofurans named wittifuran H, wittifuran I and wittifuran U (1-3) were obtained during our ongoing investigation of an ethanol extract from the stem bark of Morus wittiorum. Their structures were elucidated on the basis of spectroscopic data. Compound 2 displayed potent anti-inflammatory activity and selective cytotoxicity against human gastric cancer cell line BGC-823 with an IC(50) value of 1.45μM.     

The effects of ganoderma alcohols isolated from Ganoderma lucidum on the androgen receptor binding and the growth of LNCaP cells

The effects of ganoderma alcohols isolated from ethanol extracts of Ganoderma lucidum (Fr.) Krast (Ganodermataceae) on the androgen receptor binding and the growth of LNCaP cells have been investigated. Less than two hydroxyl groups in 17β-side chain are needed for binding to androgen receptor. In the case of the ganoderma alcohols with the same number of hydroxyl groups in 17β-side chain, the one which has C-3 carbonyl group showed better binding activity to androgen receptor than that which has C-3 hydroxyl group. The unsaturation in 17β-side chain is needed for the inhibition of the cell proliferation of androgen-induced LNCaP cells growth.     

Five new furostanol saponins from the rhizomes of Tupistra chinensis

Five new furostanol saponins (1-5), together with three known compounds (6-8) were obtained from the n-butanol soluble fraction of ethanol extract from Tupistra chinensis. Their structures were determined on the basis of chemical methods and spectral data. The isolated compounds were tested in vitro for their cytotoxic activities against the A549, HepG 2 and Caski cancer cell lines. Among them, compounds 6, 7, and 8 showed cytotoxicity against A549 cancer cell lines with IC(50) values of 6.6, 6.7 and 29.1 μM, respectively.     

Cycloartane triterpenoids from the stems of Schisandra glaucescens and their bioactivity

Five new cycloartane triterpenoids, schiglausins K-O (1-5), including one hexanortriterpenoid (1) and one octanortriterpenoid (2), as well as two known compounds (6-7), were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR spectra. Compounds 2-7 were tested for their FXR agonistic and antagonistic effects. Compound 7 exhibited significant antagonistic effect against FXR with IC(50) of 1.50 μM.     

New sesquiterpenoids from the dried flower buds of Tussilago farfara and their inhibition on NO production in LPS-induced RAW264.7 cells

Three new sesquiterpenoids, 1α-(3″-ethyl-cis-crotonoyloxy)-8-angeloyloxy-3β,4β-epoxy-bisabola-7(14),10-diene (1), 7β-angeloyloxy-14-hydroxy-notonipetranone (2) and 1α-hydroxy-7β-(4-methylsenecioyloxy)-oplopa-3(14)Z,8(10)-dien-2-one (3) were isolated from ethanolic extract of the dried flower buds of Tussilago farfara L., along with nine known sesquiterpenoids (4-12). All of these compounds were evaluated for their effect on the inhibition of nitric oxide (NO) production induced by lipopolysaccharide in macrophage cell line RAW 264.7 and exhibited inhibitory activity on NO production in a dose-dependent manner. 7β-(4-Methylsenecioyloxy)-oplopa-3(14)E,8(10)-dien-2-one (8) was proved to be the best among these tested sesquiterpenoids with an IC(50) value of 10.80 μM.     

Triterpenes and steroids from the leaves of Aglaia exima (Meliaceae)

A study on the leaves of Aglaia exima led to the isolation of one new and seven known compounds: six triterpenoids and two steroids. Their structures were elucidated and analyzed mainly by using spectroscopic methods; 1D and 2D NMR, mass spectrometry, UV spectrometry and X-ray. All the triterpenoids and steroids were measured in vitro for their cytotoxic activities against eight cancer cell lines; lung (A549), prostate (DU-145), skin (SK-MEL-5), pancreatic (BxPC-3), liver (Hep G2), colon (HT-29), breast (MCF-7) and (MDA-MB-231). The new cycloartane triterpenoid, 24(E)-cycloart-24-ene-26-ol-3-one 1, showed potent cytotoxic activity against colon (HT-29) cancer cell line (IC₅₀ 11.5 μM).     

Phenolics from Leontopodium leontopodioides inhibiting nitric oxide production

Two new compounds, a neolignan (1), and a benzofuran derivative (2), along with 6 known compounds (3-8), were isolated from the aerial parts of Leontopodium leontopodioides. The structures of the new compounds were elucidated as (7R,8S)-3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol (1) and (2R)-12-hydoxy-4-methoxy-tremeton (2) on the basis of their spectroscopic data, respectively. All of the isolates were evaluated for their effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 macrophages and compounds 1 and 8 exhibited inhibitory activity with IC(50) values of 35.80 and 24.41 μM, respectively.     

Antiviral and cytotoxic activities of some Indonesian plants

Ten methanolic extracts from eight Indonesian medicinal plants were phytochemically screened and evaluated for antiviral (HSV-1 and Poliovirus) and cytotoxic activities on murine and human cancer lines (3LL, L1210, K562, U251, DU145, MCF-7). Besides Melastoma malabathricum (Melastomataceae), the Indonesian Loranthaceae species among which Elytranthe tubaeflora, E. maingayi, E. globosa and Scurrula ferruginea exhibited attractive antiviral and cytotoxic activities. Piper aduncum (Piperaceae) was found active on Poliovirus. S. ferruginea was selected for further studies because of its activity on the U251 glioblastoma cells.     

Cytotoxic ellagitannins from Reaumuria vermiculata

Three ellagitannins and one disulfated flavonol were isolated from the aerial parts of Reaumuria vermiculata L. Besides that, 16 known compounds were characterized as well. The structures of all compounds were elucidated on the basis of spectroscopic data including 1D and 2D NMR and ESI HR-FTMS. The in vivo antioxidant activity using the oxygen radical absorbance capacity (ORAC) method, of the extract, its column fractions and two of the isolated ellagitannins was accomplished. In addition, a possible cytotoxicity of the extract and two of the new ellagitannins on HaCaT human keratinocytes and the activity of both compounds against the prostate cancer cell line (PC-3) were also assessed, whereby a potent cytotoxicity with IC(50) less than 1μg/ml was determined for both compounds. Besides, the extract exhibited a potential cytotoxic effect against four different solid tumor cell lines, namely liver (Huh-7), colorectal (HCT-116), breast (MCF-7) and prostate (PC-3). The IC(50)s were found to be substantially low (ranged from 1.3±0.15 to 2.4±0.22μg/ml) with relatively low resistance possibility reaching to 0% in the case of Huh-7 cell.