4-X-N-Y-6-氮杂雄-17-羰基-Z-4-烯-3-酮衍生物对3BHSD的抑制活性与结构关系的研究

应用分子力学方法MM,和半经验量子化学AM1法,获得22种4-X-N-Y-6-氮杂雄-17-羰基-Z-4-烯-3-酮衍生物的优势构象,再利用量子化学算法和分子图形学技术,获得电子结构参数和几何结构参数,采用多元线性回归分析和人工神经网络误差反传算法(BP),将这些参数和衍生物对3β-羟类固醇脱氢酶(3BHSD)的抑制活性相关联。结果表明,衍生物对3BHSD的抑制活性大小和分子最高占用轨道能(E_(HOMO))、16号碳原子的净电荷(Q)及5号碳原子和6号氮原子间键长的相关性较好,成功地建立了22种衍生物的构效关系式。HOMO轨道组成分析表明,A环上的4号、5号碳原子和羰基氧原子(O_(1(?)))及B环上的6号氮原子和7号碳原子可能是与受体作用时的活性位点。

Study on the relationships between the structure and inhibition activity of 4-X-N-Y-6-azaandrost-17-CO-Z-4-en-3-ones toward 3BHSD

To analyze the QSAB of 22 4-X-N-Y-6-azaandrost-17-CO-Z-4-en-3-ones,MM_ molecular mechanics method and semi-em- pirical AM1 method had been performed.Using multivariate regression analysis(MLB) and standard back-propagation algorithm of arti- ficial neural network(BP),we obtained a significant QSAR.It could be concluded as bellows:the inhibition activity of 4-X-N-Y-6- Azaandrost-17-CO-Z-4-en-3-ones toward 3BHSD were highly correlated with the highest occupied orbital energy,net charge of C_(16) and the bond length between C_5 and N_6.Successful QSAR with correlation for 22 4-X-N-Y-6-azaandrost-17-CO-Z-4-en-3-ones was devel- oped.The analysis of HOMO of 4-X-N-Y-6-azaandrost-17-CO-Z-4-en-3-ones indicated that the C_4,the C_5 and the O_(18) of ring A togeth- er with the N_6 and the C_7 of ring B might be active centers that influenced acceptors.