QSAR Study and Molecular Design of Quinonlone Carboxylic Acid Derivatives Based on Topomer CoMFA Method

KeyWord:three dimensional quantitative structure-activity relationship£¨3D-QSAR£©  quinolone carboxylic acid derivatives  Topomer CoMFA  molecular design  molecular docking

Abstract:

      The 3D-QSAR relationships of a series of quinolone carboxylic acid derivatives were studied by Topomer CoMFA technique based on R group search.The interaction validation coefficient£¨q2£©,the non cross correlation coefficient£¨r2£© and the external validation coefficiont£¨r2pred£© were 0ª±790,0ª±890 and 0ª±878£¬respectively.The results showed that the model had a good stability and a prediction ability.Topomer search was used to virtually screen lead like compounds in the ZINC molecular database.As a result,6 Ra groups and 3 Rb groups with higher contribution values were selected.12 new quinolone carboxylic acid compounds with higher predicted activity were designed.By using molecular docking,the action mechanism of drug and acceptor was studied,and the results showed that the drug functioned obviously with ASP 30,ASP 29 and ASN 25 sites of protease.The QSAR study could provide a theoretical reference for the synthesis of new drugs.