Cytochromes P450 are key enzymes for steroid hormone biosynthesis in human body. They are considered as targets for the screening of novel high efficient drugs. The results of screening of bile acids and androstane derivatives toward human recombinant steroid 17α-hydroxylase/17,20-lyase (CYP17A1) are presented in this paper. A group of steroids, binding with micromolar or submicromolar affinity (in a range from 9 μM – less than 0.1 μM), was identified. Results presented here showed that these steroidal compounds are able to decrease rate of hydroxylation of essential CYP17A1 substrate – progesterone, while some compounds completely inhibited enzyme activity. Structure-activity relationship (SAR) analysis based on in vitro and in silico studies showed that high affinity of the enzyme to bile acids derivatives is correlated with side chain hydrophobicity and presence of hydroxyl or keto group at C₃ position. From the other side, bile acid-derived compounds with more polar side chain or substituents at C₇ and C₁₂ positions possess higher K_d values. Among androstane-derived steroids couple of Δ⁵-steroids with hydroxyl group at C₃ position, as well as 16,17-secosteroids, were found to be high affinity ligands of this enzyme. The data obtained could be useful for the design of novel highly efficient inhibitors of CYP17A1, since the bile acids-derived compounds are for first time recognized as effective CYP17A1 inhibitors.

细胞色素P450是人体中类固醇激素生物合成的关键酶。它们被认为是筛选新型高效药物的目标。本文介绍了针对人重组类固醇17α-羟化酶/ 17,20-裂合酶（CYP17A1）的胆汁酸和雄甾烷衍生物的筛选结果。鉴定了一组与微摩尔或亚微摩尔亲和力结合的类固醇（范围从9μM到小于0.1μM）。此处显示的结果表明，这些甾体化合物能够降低必需的CYP17A1底物孕酮的羟化速率，而某些化合物完全抑制酶的活性。基于体外和计算机模拟的结构-活性关系（SAR）分析研究表明，该酶对胆汁酸衍生物的高亲和力与侧链疏水性以及C ₃位上羟基或酮基的存在有关。另一方面，在C ₇和C ₁₂位置具有更多极性侧链或取代基的胆汁酸衍生化合物具有较高的K _d值。间雄甾烷衍生的类固醇夫妇Δ的⁵中C -steroids与羟基₃位置，以及16,17-secosteroids，被发现是这种酶的高亲和力配体。获得的数据可能对设计新型高效CYP17A1抑制剂有用，因为胆汁酸衍生的化合物首次被认为是有效的CYP17A1抑制剂。