Biotransformation studies of prednisone using human intestinal bacteria Part II: Anaerobic incubation and docking studies

Abstract

Anaerobic incubation of prednisone 1 with human intestinal bacteria (HIB) afforded nine metabolites: 5β-androst-1-ene-3,11,17-trione 3, 3α-hydroxy-5α-androstane-11,17-dione 4, 3β,17α,20- trihydroxy-5α-pregnan-11-one 5, 3α,17α-dihydroxy-5α- pregnane-11,20-dione 6, 3α,17α-dihydroxy-5β-pregnane-11,20- dione 7, 3β,17β-dihydroxy-5α-androstan-11-one 8β, 3β,17α-dihydroxy-5α-androstan-11-one 8α, 3α,17β-dihydroxy-5α-androstan-11-one 9β, and 3α,17α-dihydroxy-5α-androstan-11-one 9α. The structures of these metabolites (39) were elucidated using several spectroscopic techniques. Computer-aided prediction of potential biological activities of the isolated prednisone metabolites (39) revealed potential inhibition of prostaglandin E2 9-ketoreductase (PGE2 9-KR). Docking studies applied to PGE2 9-KR allowed recommendation of the metabolites 4, 8β, and 8α for further pharmacological study as PGE2 9-KR inhibitors. © 2009 Informa UK Ltd.