Department of Pharmaceutical Medicinal Chemistry, Assiut University, Assiut, Egypt.
J Enzyme Inhib Med Chem. 2009 Dec;24(6):1211-9. doi: 10.3109/14756360902781322.
Anaerobic incubation of prednisone 1 with human intestinal bacteria (HIB) afforded nine metabolites: 5beta-androst-1-ene-3,11,17-trione 3, 3alpha-hydroxy-5alpha-androstane-11,17-dione 4, 3beta,17alpha,20-trihydroxy-5alpha-pregnan-11-one 5, 3alpha,17alpha-dihydroxy-5alpha-pregnane-11,20-dione 6, 3alpha,17alpha-dihydroxy-5beta-pregnane-11,20-dione 7, 3beta,17beta-dihydroxy-5alpha-androstan-11-one 8beta, 3beta,17alpha-dihydroxy-5alpha-androstan-11-one 8alpha, 3alpha,17beta-dihydroxy-5alpha-androstan-11-one 9beta, and 3alpha,17alpha-dihydroxy-5alpha-androstan-11-one 9alpha. 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, 8beta, and 8alpha for further pharmacological study as PGE2 9-KR inhibitors.
将泼尼松龙 1 与人体肠道细菌（HIB）进行厌氧孵育，得到了 9 种代谢产物：5β-雄甾-1-烯-3,11,17-三酮 3、3α-羟基-5α-雄烷-11,17-二酮 4、3β,17α,20-三羟基-5α-孕甾-11-酮 5、3α,17α-二羟基-5α-孕烷-11,20-二酮 6、3α,17α-二羟基-5β-孕烷-11,20-二酮 7、3β,17β-二羟基-5α-雄烷-11-酮 8β、3β,17α-二羟基-5α-雄烷-11-酮 8α、3α,17β-二羟基-5α-雄烷-11-酮 9β 和 3α,17α-二羟基-5α-雄烷-11-酮 9α。这些代谢产物（3-9）的结构通过几种光谱技术进行了阐明。计算机辅助预测分离出的泼尼松龙代谢产物（3-9）的潜在生物学活性表明，它们可能抑制前列腺素 E2 9-酮还原酶（PGE2 9-KR）。应用于 PGE2 9-KR 的对接研究推荐了代谢产物 4、8β 和 8α 作为进一步药理学研究的 PGE2 9-KR 抑制剂。
