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

• 来源期刊: 高等学校化学研究（英文版）
• 年，卷（期）: 2019,（6）
• 页码范围: 1111-1118
• 页数: 8页
• 语种: 英文
• DOI: 10.1007/s40242-019-9183-5

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 Csp2_03_F descriptor,showed better predictive ability.Validation parameters(Q2 and R2) for the models were 0.722 and 0.925,respectively.In addition,external validation for the models using a test group revealed R2pred=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.