title: Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5α-reductase inhibitors: a legitimate approach.
abstract: In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5α-reductase inhibitory activity by measuring the conversion of [(3)H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5α-reductase II enzyme with IC(50) values of 54.1 ± 9.5, 22.1 ± 2.4, 72.8 ± 2.3 and 26.5 ± 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight.
authors: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India. aggarwalsau@gmail.com
authors: Saurabh
authors: S
authors: Aggarwal
authors: Suresh
authors: S
authors: Thareja
authors: T R
authors: TR
authors: Bhardwaj
authors: Jörg
authors: J
authors: Haupenthal
authors: R W
authors: RW
authors: Hartmann
authors: Manoj
authors: M
authors: Kumar
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000735:Androstenedione / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D060326:Chemistry Techniques, Synthetic; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors*; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058891:5-alpha Reductase Inhibitors; D007527:Isoenzymes; D000735:Androstenedione; D042944:Cholestenone 5 alpha-Reductase