Abstract: Biotransformation of an aromatase inhibitor, testolactone (1), yielded four metabolites, 7?-hydroxy-3-oxo-13,17-seco-5?-androsta-1-eno-17,13?-lactone (2), 3?,11?-dihydroxy-13,17-seco-5?-androsta-17,13?-lactone (3), 4?,5?-epoxy-3?-hydroxy-13,17-secoandrosta-1-eno-17,13?-lactone (4), and 4?,5?-epoxy-3?-hydroxy-13,17-secoandrosta-1-eno-17,13?-lactone (5). Aromatase (estrogen synthase) involves in the synthesis of estrogen, and promotes the growth of breast cancerous cells. It is a key target for the discovery of chemotherapeutic agents against ER+(estrogen-positive) breast-cancers. Metabolites 2 (IC50=8.63±0.402 nM), and 3 (IC50=9.23±1.31 nM) were identified as potent inhibitors against human aromatase enzyme, in comparison to 1 (IC50=0.716±0.031 ?M), and the standard aromatase inhibiting drug, exemestane (IC50=0.232±0.031 ?M). Derivatives 4 (IC50=10.37±0.50 ?M) and 5 (IC50=0.82±0.059 ?M) also showed a good inhibition against aromatase enzyme.

Abstract: Biotransformation of gestonorone acetate (1) with Cunninghamella blakesleeana (ATCC 8688) yielded a new analogue, 17?-actoxy-10?,11?-dihydroxy-progesterone (2). Compound 2 was identified as non-cytotoxic inhibitor of human aromatase enzyme (IC50=0.827±0.066 ?M). Compound 2 showed a significant aromatase inhibitory activity, as compared to the standard aromatase inhibitory drug, exemestane (IC50=0.232±0.03 ?M).

Abstract: The present invention identifies new steroidal analogues of formestane synthesized through biotransformation with significant aromatase inhibitory activity, and thus can serve as possible safe, effective, and selective anti-cancer agent towards estrogen-responsive (ER+) breast cancer. Four new derivatives of anticancer drug formestane (1), 4?,5?,7?-trihydroxyandrostane-3,17-dione (2), 3?,7?-dihydroxyandrostane-4,17-dione (3), 3?,5?,7?-trihydroxyandrostane-4,17-dione (4), and 4,11?-dihydroxyandrosta-1,4-diene-3,17-dione (5) were synthesized through bio-catalyzed structural modifications by Cunninghamella. blakesleeana and Fusarium lini. The new derivatives showed varying degree of inhibition of aromatase enzyme. Metabolite 4 (IC50=0.386±0.072 ?M), showed a significant inhibitory potential, comparable to substrate 1 (IC50=0.335±0.011 ?M) and standard aromatase inhibitory anti-cancer drug exemestane (IC50=0.232±0.031 ?M). Metabolites 3 (IC50=1.37±0.029 ?M), and 2 (IC50=5.229±0.

Abstract: Four new analogues, 17?-hydroxy-7?,17?-dimethylestr-4,6-diene-3-one (2), 11?,17?-dihydroxy-7?, 17?-dimethyl-estra-1,3,5-triene-3-one (3), 3?,10?,17?-trihydroxy-7?,17?-dimethyl-5?-estrane (4), and 17?-hydroxy-7?,17?-dimethyl-5?-estrane-3,6-dione (5) of anabolic drug mibolerone (1) were synthesized. Derivatives 2 (IC50=3.83 ±0.3 ?M) and 3 (IC50=4.24 ±0.2 ?M) were identified as potent anti-inflammatory agents against T-cell proliferation. Derivative 4 (IC50=28.5 ±0.07 ?M) showed a potent anti-inflammatory activity against TNF-? production. In addition, compounds 1 (IC50=46.0 ±2.4 ?M), 2 (IC50=54.4 ±0.3 ?M), 3 (IC50=49.1 ±0.4 ?M), 4 (IC50=58.0 ±0.1 ?M) and 5 (IC50=52.7 ±0.3 ?M) showed a remarkable anti-inflammatory activity against NO? production. Metabolite 4 (IC50=0.072 ±0.001 ?M) showed a potent inhibitory activity against human placental aromatase. Compound 1 (IC50=24.19 ±2.1 ?g/mL) was found to be cytotoxic against BJ normal cell line, while metabolites 2-5 were identified as non-cytotoxic.

Abstract: New analogues of anti-cancer drugs atamestane (1), drostanolone enanthate ((3), and exemestane (6) were synthesized through biotransformation. New derivatives, 14?-hydroxy-1-methylandrosta-1,4-diene-3,17-dione ((2) (IC50, 9.7±0.72 nM) of 1 (IC50, 13.8±0.2 nM), and 2-methylandrosta-12?,17?-dihydroxy-1,4-diene-3-one (4) (IC50, 4.23±0.133 nM) of 3 (IC50, 6.4±0.06 nM) showed a potent inhibition against human aromatase enzyme and thus have the potential to treat ER+ breast-cancers and other related diseases. New metabolites, 2?-methyl-9?,17?-dihydroxy-5?-androstan-3-one ((5) (IC50=793.0±29.9 nM) of 3, 6-methylene-3?,7?,17?-trihydroxy-5?-androstane (7) (IC50, 46.1±0.81 nM), and 11?,17?-dihydroxy-6-methylene-androsta-1,4-diene-3-one (8) (IC5O=12797.0±844 nM) of exemestane (6) (IC50=232.0±31 nM) also showed a remarkable anti-aromatase activity. Aromatase is an enzyme, involves in the synthesis of estrogen (ER).

Abstract: Biotransformation of an aromatase inhibitor, testolactone (1), yielded five new metabolites, 7?-hydroxy-3-oxo-13,17-secoandrosta-1,4-dieno-17,13?-lactone (2), 7?-hydroxy-3-oxo-13,17-seco-5?-androsta-1-eno-17,13?-lactone (3), 3?,11?-dihydroxy-13,17-seco-5?-androsta-17,13?-lactone (4), 4?,5?-epoxy-3?-hydroxy-13,17-secoandrosta-1-eno-17,13?-lactone (5), and 4?,5?-epoxy-3?-hydroxy-13,17-secoandrosta-1-eno-17,13?-lactone (6). Aromatase (estrogen synthase) involves in the synthesis of estrogen, and promotes the growth of breast cancerous cells. It is a key target for the discovery of chemotherapeutic agents against ER+ (estrogen-positive) breast-cancers and several other diseases caused by overexpression of aromatase enzyme. Metabolites 3 (IC50=8.60±0.402 nM), and 4 (IC50=9.23±1.31 nM) were identified as potent inhibitors against human aromatase enzyme, in comparison to 1 (IC50=0.716±0.031 ?M), and the standard aromatase inhibiting drug, exemestane (IC50=0.232±0.031 ?M). Derivatives 2 (IC50=11.68±0.

Abstract: The invention relates to a method of identifying inhibitors against target receptor ?-glucoronidase. Three compounds were found to be completely non-cytotoxic while, the remaining compounds showed moderate cytotoxicity.

Abstract: Quinazoline derivatives 1-25, (2-[3,4-bis(methyloxy)phenyl]quinazolin-4-(3H)-one) and 2-[2-(ethyloxy)phenyl]quinazoline-4-(3H)-one) are reported as ?-glucuronidase inhibitors useful in the treatment of ?-glucuronidase hyperactivity disorders.