HIV-1逆转录酶抑制剂的三维定量构效关系  

3D-QSAR for HIV-1 reverse transcriptase inhibitors

作　　者：谢惠定[1,2] 邱开雄[2] 谢小光[1] 付继军[2] 

机构地区：[1]云南大学化学科学与工程学院,云南昆明650091 [2]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500

出　　处：《分子科学学报》2015年第4期315-320,共6页Journal of Molecular Science

基　　金：云南省应用研究基础计划项目(2011FZ096)

摘　　要：采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA)对一系列非核苷类HIV-1逆转录酶抑制剂(苯磺酰基亚胺噻唑类化合物)进行了三维定量构效关系的研究,获得了高可靠性的CoMFA和CoMSIA模型,其交叉验证相关系数q2值分别为0.748和0.607.通过对CoMFA和CoMSIA模型三维等势图的分析,确定了该类化合物抗HIV-1活性的结构要求.研究结果表明,对苯磺酰基亚胺噻唑类化合物而言,在苯环的C-5位引入体积大和电负性强的基团能增加其抑制活性;苯环的C-2位的氢键给体基团对活性有利;噻唑环的R2取代基疏水性增大会降低生物活性.研究结果表明,可以指导新HIV-1逆转录酶抑制剂的设计和合成.A 3D-QSAR study of a series of HIV-1non-nucleoside reverse transcriptase（RT）inhibitors（thiazolidenebenzenesulfonamide derivatives）was carried out by comparative molecular field analysis（CoMFA）and comparative molecular similarity indices analysis（CoMSIA）methods,and highly reliable and predictive CoMFA and CoMSIA models with cross-validated q2 values of 0.748 and 0.607,respectively,were obtained.The CoMFA and CoMSIA contour maps were analyzed in detail to better understand the structural requirements for inhibitory activity against HIV-1.The results show that for thiazolidenebenzenesulfonamide inhibitors,bulky and electronegative groups in C-5position of the benzene ring are required to have high inhibitory activity.Moreover,H-bond donor groups in C-2position of the benzene ring are favorable to inhibitory activity while hydrophobic groups near the R2 group of the thiazole ring are unfavorable.The results in the present study can provide help for design and synthesize new HIV-1inhibitors with higher activity.

关 键 词：比较分子力场分析法 比较分子相似性指数分析法 HIV-1逆转录酶 苯磺酰基亚胺噻唑类化合物 

分 类 号：O643[理学—物理化学]