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Chemical Research in Chinese Universities

, Volume 35, Issue 6, pp 1111–1118 | Cite as

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

  • Xiaoyi ZhangEmail author
  • Wenling Niu
  • Tang Tang
  • Chengfei Hou
  • Yajie Guo
  • Ren Kong
Article
  • 15 Downloads

Abstract

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 \(R_{\rm{pred}}^2=0.892\). 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.

Keywords

Diketo acid(DKA) Modified quantitative structure-activity relationship(QSAR) Autodock Drug design Descriptor screening 

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Supplementary material

40242_2019_9183_MOESM1_ESM.pdf (257 kb)
A Strategy to Find Novel Candidate DKAs Inhibitors Using Modified QSAR Model with Favorable Druggability Properties

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Copyright information

© Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH 2019

Authors and Affiliations

  • Xiaoyi Zhang
    • 1
    Email author
  • Wenling Niu
    • 1
  • Tang Tang
    • 1
  • Chengfei Hou
    • 1
  • Yajie Guo
    • 1
  • Ren Kong
    • 2
  1. 1.College of Life Science and BioengineeringBeijing University of TechnologyBeijingP. R. China
  2. 2.Institute of Bioinformatics and Medical Engineering, School of Electrical and Information EngineeringJiangsu University of TechnologyChangzhouP. R. China

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