A Strategy to Find Novel Candidate DKAs Inhibitors Using Modified QSAR Model with Favorable Druggability Properties  

作　　者：ZHANG Xiaoyi NIU Wenling TANG Tang HOU Chengfei GUO Yajie KONG Ren 

机构地区：[1]College of Life Science and Bioengineering,Beijing University of Technology,Beijing 100124,P.R.China [2]Institute of Bioinfotmatics and Medical Engineering,School of Electrical and Information Engineering,Jiangsu University of Technology,Changzhou 213016,P.R.China

出　　处：《Chemical Research in Chinese Universities》2019年第6期1111-1118,共8页高等学校化学研究（英文版）

基　　金：Supported by the Project of the Beijing Municipal Commission of Education,China(No.KM201410005030);the Importation and Development of High-caliber Talents Project of Beijing Municipal Institutions,China;the National Natural Science Foundation of China(No.31100523).

摘　　要：The study dealed with quantitative structure-activity relationship(QSAR)to explore the important features of diketo acid(DKA)derivatives for exerting potent HIV-1 integrase inhibitors activity.A three-step screening method was proposed to choose descriptors.Then,additional descriptors were used in the CoMFA and CoMSIA.Lastly,a modified CoMSIA m7 model,constructed by adding Csp^2_03_F descriptor,showed better predictive ability.Validation parameters(Q^2 and R^2)for the models were 0.722 and 0.925,respectively.In addition,external validation for the models using a test group revealed R^2pred=0.892.Contour maps analysis defined favored and disfavored regions of the compounds,and two new compounds with the descriptor structure were designed with better activities than Raltegravir(RAL),well drug-likeness and low toxicity.The research provides a base for further DKA development.

关 键 词：Diketo acid(DKA) MODIFIED quantitative STRUCTURE-ACTIVITY relationship(QSAR) AUTODOCK Drug design DESCRIPTOR screening 

分 类 号：R58[医药卫生—内分泌]