Atia-tul Wahab

Nematicidal natural products from the aerial parts of Lantana camara Linn.

Lantanilic acid, camaric acid and oleanolic acid possessing nematicidal activity were isolated from the methanolic extract of the aerial parts of Lantana camara Linn. through bio-assay guided fractionation. These compounds exhibited 98%, 95% and 70% mortality respectively against root-knot nematode Meloidogyne incognita at 0.5% concentration. Conventional nematicide furadan showed 100% mortality at this concentration.

Antimycobacterial activity of flavonoids from Lantana camara Linn

Linaroside (1) and lantanoside (2), two flavonoids isolated from Lantana camara and their common acetyl derivative (3) were examined for antimycobacterial activity against Mycobacterium tuberculosis, strain H37Rv. These compounds exhibited 30, 37 and 98% inhibition, respectively at 6.25 µg mL−1 concentration. Among these flavonoids acetylated compound was found to be the most active.

Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines

BackgroundMicrobial transformation of steroids has been extensively used for the synthesis of steroidal drugs, that often yield novel analogues, not easy to obtain by chemical synthesis. We report here fungal transformation of a synthetic steroidal drug, exemestane, used for the treatment of breast cancer and function through inhibition of aromatase enzyme.ResultsMicrobial transformation of anti-cancer steroid, exemestane (1), was investigated by using two filamentous fungi. Incubation of 1 with fungi Macrophomina phaseolina, and Fusarium lini afforded three new, 11α-hydroxy-6-methylene-androsta-1, 4-diene-3,17-dione (2), 16β, 17β-dihydroxy-6-methylene-androsta-1, 4-diene-3-one (3), and 17β-hydroxy-6-methylene-androsta-1, 4-diene-3, 16-dione (4), and one known metabolites, 17β-hydroxy-6-methylene-androsta-1, 4-diene-3-one (5). Their structures were deduced spectroscopically. Compared to 1 (steroidal aromatase inactivator), the transformed metabolites were also evaluated for cytotoxic activity by using a cell viability assay against cancer cell lines (HeLa and PC3). Metabolite 2 was found to be moderately active against both the cell lines.ConclusionsBiotransformation of exemestane (1) provides an efficient method for the synthesis of new analogues of 1. The metabolites were obtained as a result of reduction of double bond and hydroxylation. The transformed product 2 exhibited a moderate activity against cancer cell lines (HeLa and PC3). These transformed products can be studied for their potential as drug candidates.

Biotransformation of 6-dehydroprogesterone with Aspergillus niger and Gibberella fujikuroi

Microbial transformation of 6-dehydroprogesterone (1) with Aspergillus niger yielded three new metabolites, including 6β-chloro-7α,11α-dihydroxypregna-4-ene-3,20-dione (2), 7α-chloro-6β,11α-dihydroxypregna-4-ene-3,20-dione (3), and 6α,7α-epoxy-11α-hydroxypregna-4-ene-3,20-dione (4), and two known metabolites; 6α,7α-epoxypregna-4-ene-3,20-dione (5), and 11α-hydroxypregna-4,6-diene-3,20-dione (6). Compounds 2, and 3 contain chlorohydrin moiety at C-6, and C-7, respectively. The biotransformation of 1 with Gibberella fujikuroi yielded a known compound, 11α,17β-dihydroxyandrosta-4,6-dien-3-one (7).

Artonin I inhibits multidrug resistance in Staphylococcus aureus and potentiates the action of inactive antibiotics in vitro.

The emergence of multidrug‐resistant (MDR) Staphylococcus aureus is a challenge for the treatment of infections. We report here the antimicrobial activity of artonin I against MDR Staph. aureus, its mechanism of reversal of resistance and synergistic effects by combinational therapy.

Biotransformation of a potent anabolic steroid, mibolerone, with Cunninghamella blakesleeana, C. echinulata, and Macrophomina phaseolina, and biological activity evaluation of its metabolites

Seven metabolites were obtained from the microbial transformation of anabolic-androgenic steroid mibolerone (1) with Cunninghamella blakesleeana, C. echinulata, and Macrophomina phaseolina. Their structures were determined as 10β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (2), 6β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (3), 6β,10β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (4), 11β,17β-dihydroxy-(20-hydroxymethyl)-7α,17α-dimethylestr-4-en-3-one (5), 1α,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (6), 1α,11β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (7), and 11β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (8), on the basis of spectroscopic studies. All metabolites, except 8, were identified as new compounds. This study indicates that C. blakesleeana, and C. echinulata are able to catalyze hydroxylation at allylic positions, while M. phaseolina can catalyze hydroxylation of CH2 and CH3 groups of substrate 1. Mibolerone (1) was found to be a moderate inhibitor of β-glucuronidase enzyme (IC50 = 42.98 ± 1.24 μM) during random biological screening, while its metabolites 2–4, and 8 were found to be inactive. Mibolerone (1) was also found to be significantly active against Leishmania major promastigotes (IC50 = 29.64 ± 0.88 μM). Its transformed products 3 (IC50 = 79.09 ± 0.06 μM), and 8 (IC50 = 70.09 ± 0.05 μM) showed a weak leishmanicidal activity, while 2 and 4 were found to be inactive. In addition, substrate 1 (IC50 = 35.7 ± 4.46 μM), and its metabolite 8 (IC50 = 34.16 ± 5.3 μM) exhibited potent cytotoxicity against HeLa cancer cell line (human cervical carcinoma). Metabolite 2 (IC50 = 46.5 ± 5.4 μM) also showed a significant cytotoxicity, while 3 (IC50 = 107.8 ± 4.0 μM) and 4 (IC50 = 152.5 ± 2.15 μM) showed weak cytotoxicity against HeLa cancer cell line. Compound 1 (IC50 = 46.3 ± 11.7 μM), and its transformed products 2 (IC50 = 43.3 ± 7.7 μM), 3 (IC50 = 65.6 ± 2.5 μM), and 4 (IC50 = 89.4 ± 2.7 μM) were also found to be moderately toxic to 3T3 cell line (mouse fibroblast). Interestingly, metabolite 8 showed no cytotoxicity against 3T3 cell line. Compounds 1–4, and 8 were also evaluated for inhibition of tyrosinase, carbonic anhydrase, and α-glucosidase enzymes, and all were found to be inactive.

Microbial-catalysed derivatization of anti-cancer drug exemestane and cytotoxicity of resulting metabolites against human breast adenocarcinoma cell line (MCF-7) in vitro

Structural transformation of anticancer drug exemestane (1) with fungi Cunninghamella blakesleeana (ATCC 8688A), Curvularia lunata (ATCC 12017), Aspergillus niger (ATCC 10549), and Gibberella fujikuroi (ATCC 10704) yielded eleven metabolites 2-12, in which 2 and 8 were identified as new. Their structures were characterized as 6-methylene-5α-androstane-3β,16β,17β-triol (2), 17β-hydroxy-6-methyleneandrosta-4-ene-3-one (3), 6α-spiroxirandrost-4-ene-3,17-dione (4), 6-methyleneandrosta-4-ene-3,17-dione (5), 6β,17β-dihydroxyandrost-4-en-3-one (6), 17β-hydroxy-6α-spiroxirandrost-1,4-diene-3-one (7), 17β-hydroxy-6α-hydroxymethylandrosta-1,4-dien-3-one (8), 6α-hydroxymethylandrosta-1,4-diene-3,17-dione (9), 17β-hydroxy-6-methyleneandrosta-1,4-diene-3,16-dione (10), 6α-hydroxy-4-androstene-3,17-dione (11), and 6α-hydroxymethylandrost-4-ene-3,17-dione (12). Substrate 1, and its transformed products were evaluated for their cytotoxicity against breast cancer cell line (MCF-7). Compound 3 was found to be moderately active with an IC50 of 33.43±4.01μM, in comparison to the standard anti-cancer drug, doxorubicin (IC50=0.92±0.1μM).

Two new prenylated flavonoids from the roots of Berberis thunbergii DC.

Abstract Two new prenylated flavonoids, thunbergiols A (1) and B (2), along with three known compounds, chrysin (3), quercetin (4) and berberine (5) were obtained from the methanolic extract of roots of Berberis thunbergii DC. MS, NMR and other spectroscopic techniques were employed for their structural characterisation.

Microbial transformation of contraceptive drug etonogestrel into new metabolites with Cunninghamella blakesleeana and Cunninghamella echinulata.

Biotransformation of a steroidal contraceptive drug, etonogestrel (1), (13-ethyl-17β-hydroxy-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3-one) was investigated with Cunninghamella blakesleeana and C. echinulata. Five metabolites 2-6 were obtained on incubation of 1 with Cunninghamella blakesleeana, and three metabolites, 2, 4, and 6 were isolated from the transformation of 1 with C. echinulata. Among them, metabolites 2-4 were identified as new compounds. Their structures were deduced as 6β-hydroxy-11,22-epoxy-etonogestrel (2), 11,22-epoxy-etonogestrel (3), 10β-hydroxy-etonogestrel (4), 6β-hydroxy-etonogestrel (5), and 14α-hydroxy-etonogestrel (6). Compounds 1-6 were evaluated for various biological activities. Interestingly, compound 5 was found to be active against β-glucuronidase enzyme with IC50 value of 13.97±0.12μM, in comparison to standard compound, d-saccharic acid 1,4-lactone (IC50=45.75±2.16μM). Intestinal bacteria produce β-glucuronidase. Increased activity of β-glucuronidase is responsible for the hydrolyses of glucuronic acid conjugates of estrogen and other toxic substances in the colon, which plays a key role in the etiology of colon cancer. Inhibition of β-glucoronidase enzyme therefore has a therapeutic significance. Compounds 1-6 were also found to be non cytotoxic against 3T3 mouse fibroblast cell lines.