University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Eur J Med Chem. 2010 Feb;45(2):476-81. doi: 10.1016/j.ejmech.2009.10.030. Epub 2009 Oct 28.
Azasteroids have been reported as inhibitors of human 5alpha-reductase enzyme. These were designed by substitution of one carbon atom of steroidal A ring by heteroatom nitrogen. Due to lack of information on the crystal structure of human 5alpha-reductase, 3D-QSAR study has been performed on a series of unsaturated 4-azasteroids using Self Organizing Molecular Field Analysis (SOMFA) for rationalizing the molecular properties and human 5alpha-reductase inhibitory activities. The statistical results having good cross-validated r(2)(cv) (0.783), non cross-validated r(2) (0.806) and F-test value (87.282), showed satisfied predictive ability. Analysis of SOMFA models through electrostatic and shape grids provide useful information for the design and optimization of new steroidal human 5alpha-reductase inhibitors.
已报道阿扎甾体化合物可抑制人 5α-还原酶。这些化合物通过甾体 A 环的一个碳原子被杂原子氮取代而设计得到。由于缺乏人 5α-还原酶晶体结构的信息，因此对一系列不饱和 4-氮杂甾体化合物进行了 3D-QSAR 研究，使用自组织分子场分析（SOMFA）来合理化分子性质和人 5α-还原酶抑制活性。统计结果具有良好的交叉验证 r(2)(cv)（0.783）、非交叉验证 r(2)（0.806）和 F 检验值（87.282），表明具有令人满意的预测能力。通过静电和形状网格对 SOMFA 模型进行分析，为新的甾体人 5α-还原酶抑制剂的设计和优化提供了有用信息。
