title: Steroidal carbonitriles as potential aromatase inhibitors.
abstract: Estrogens, responsible for the growth of hormone-dependant breast cancer are biosynthesized from androgens involving aromatase enzyme in the last rate limiting step. Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. Novel 4-phenylthia derivatives (2, 3 and 7) have been synthesized as aromatase inhibitors. The synthesized compounds (2, 3 and 7) exhibited noticeable enzyme inhibiting activity. Kinetics study of these compounds (2, 3, and 7) showed negligible inhibition of the enzyme under conditions conducive for irreversible inhibition of the enzyme. Introduction of unsaturation at C-4, C-1 & 4 or C-4 & 6 (compounds 5, 9 and 11) was observed to not be an effective strategy for entrancing aromatase inhibiting activity in 17-oxo-16β-carbonitrile derivatives. The D-seco derivatives (13-15 and 17) having unsaturation at C-4, C-1 & 4 or C-4 & 6 along with carbonitrile function in ring-D showed complete loss of aromatase inhibiting activity.
authors.affiliation: Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The MS University of Baroda, Vadodara, India. mryadav11@yahoo.co.in
authors.forename: Mange Ram
authors.initials: MR
authors.lastname: Yadav
authors.forename: Prafulla M
authors.initials: PM
authors.lastname: Sabale
authors.forename: Rajani
authors.initials: R
authors.lastname: Giridhar
authors.forename: Christina
authors.initials: C
authors.lastname: Zimmer
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D001378:Azasteroids / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D015394:Molecular Structure
chemical_list: D047072:Aromatase Inhibitors; D001378:Azasteroids; D001141:Aromatase