CCR5小分子拮抗剂结构与抗HIV活性构效关系的研究

发布时间：2018-11-01 11:45

【摘要】：目的本文针对51个具有CCR5拮抗剂作用的咪唑并吡啶衍生化合物进行构效关系研究,希望能够为设计此类小分子药物提供依据。方法运用比较分子力场分析(Co MFA)和比较分子相似性指数分析(Co MSIA)这2种经典的三维定量构效关系(3D-QSAR)方法,分别建立了相应的模型,进行分子结构和抗病毒活性彼此关系的分析。结果 Co MFA模型的交叉验证系数q~2和相关系数r~2分别为0.617和0.825,立体场和静电场对活性的贡献为62%和38%;Co MSIA模型的交叉验证系数q~2和相关系数r~2分别为0.599和0.810,立体场、静电场、疏水场、氢键供体场和受体场对活性的贡献分别为9.8%、12.5%、33.8%、30.8%和13.1%。结论这2种模型都显示出了较好的预测性和稳定性,其三维等势图也证实了这些化合物拮抗CCR5的构效关系。
[Abstract]:Objective to study the structure-activity relationship of 51 imidazolopyridine derivatives with CCR5 antagonist in order to provide basis for the design of these small molecular drugs. Methods using comparative molecular force field analysis (Co MFA) and comparative molecular similarity index (Co MSIA), two classical three-dimensional quantitative structure-activity relationships (3D-QSAR) methods were established. The relationship between molecular structure and antiviral activity was analyzed. Results the cross validation coefficients (Q2) and correlation coefficients (rn2) of Co MFA model were 0.617 and 0.825, respectively. The contribution of stereoscopic and electrostatic fields to the activity was 62% and 38%, respectively. The cross validation coefficients of Co MSIA model Q2 and correlation coefficient rn2 were 0.599 and 0.810, respectively. The contribution of stereoscopic field, electrostatic field, hydrophobic field, hydrogen bond donor field and acceptor field to the activity was 9.80.12.5and 33.8respectively. 30.8% and 13.1%. Conclusion these two models showed good predictability and stability, and their three-dimensional isopotential diagrams also confirmed the structure-activity relationship of these compounds antagonizing CCR5.
【作者单位】：重庆理工大学药学与生物工程学院;重庆大学化学化工学院;重庆理工大学化工学院;
【基金】：国家自然科学基金(81171508,31170747) 重庆市自然科学基金重点项目(CSTC2013JJB10064,CSTC2015JCYJBX0080) 重庆市教委科技项目(KJ130809,KJ1400946)
【分类号】：R914

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