Abstract
Anaerobic incubation of prednisone 1 with human intestinal bacteria (HIB) afforded nine metabolites: 5 beta-androst-1-ene-3,11,17-trione 3, 3 alpha-hydroxy-5 alpha-androstane-11,17-dione 4, 3 beta, 17 alpha, 20-trihydroxy-5 alpha-pregnan-11-one 5, 3 alpha, 17 alpha-dihydroxy-5 alpha-pregnane-11,20-dione 6, 3 alpha,17 alpha-dihydroxy-5 beta-pregnane-11,20-dione 7, 3 beta,17 beta-dihydroxy-5 alpha-androstan-11-one 8 beta, 3 beta, 17 alpha-dihydroxy-5 alpha-androstan-11-one 8 alpha, 3 alpha, 17 beta-dihydroxy-5 alpha-androstan-11-one 9 beta, and 3 alpha,17 alpha-dihydroxy-5 alpha-androstan-11-one 9 alpha. The structures of these metabolites (3-9) were elucidated using several spectroscopic techniques. Computer-aided prediction of potential biological activities of the isolated prednisone metabolites (3-9) revealed potential inhibition of prostaglandin E2 9-ketoreductase (PGE2 9-KR). Docking studies applied to PGE2 9-KR allowed recommendation of the metabolites 4, 8 beta, and 8 alpha for further pharmacological study as PGE2 9-KR inhibitors.