Biotransformation of an aromatase inhibitor, testolactone (1), yielded five new metabolites, 7α-hydroxy-3-oxo-13,17-secoandrosta-1,4-dieno-17,13α-lactone (2), 7β-hydroxy-3-oxo-13,17-seco-5β-androsta-1-eno-17,13α-lactone (3), 3α,11β-dihydroxy-13,17-seco-5β-androsta-17,13α-lactone (4), 4β,5β-epoxy-3β-hydroxy-13,17-secoandrosta-1-eno-17,13α-lactone (5), and 4β,5β-epoxy-3α-hydroxy-13,17-secoandrosta-1-eno-17,13α-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 (IC.sub.50=8.60±0.402 nM), and 4 (IC.sub.50=9.23±1.31 nM) were identified as potent inhibitors against human aromatase enzyme, in comparison to 1 (IC.sub.50=0.716±0.031 μM), and the standard aromatase inhibiting drug, exemestane (IC.sub.50=0.232±0.031 μM). Derivatives 2 (IC.sub.50=11.68±0.73 μM), 5 (IC.sub.50=10.37±0.50 μM) and 6 (IC.sub.50=0.82±0.059 μM) have also a good inhibition against aromatase enzyme. Therefore, metabolites 2-6 have the potential to serve as therapeutic agents against diseases caused by aromatase enzyme, including breast cancer.

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 (IC.sub.50=8.63?0.402 nM), and 3 (IC.sub.50=9.23?1.31 nM) were identified as potent inhibitors against human aromatase enzyme, in comparison to 1 (IC.sub.50=0.716?0.031 ?M), and the standard aromatase inhibiting drug, exemestane (IC.sub.50=0.232?0.031 ?M). Derivatives 4 (IC.sub.50=10.37?0.50 ?M) and 5 (IC.sub.50=0.82?0.059 ?M) also showed a good inhibition against aromatase enzyme. Therefore, metabolites 2-5 have the potential to serve as therapeutic agents against ER+ (estrogen-positive) breast-cancers.