통합자연과학논문집 (Journal of Integrative Natural Science)

조선대학교 기초과학연구원 (The Basic Science Institute Chosun University)
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Fragment based QSAR Analysis of CXCR-2 Inhibitors Using Topomer CoMFA Approach

  • Thirumurthy, M (Department of Genetic Engineering, School of Bioengineering, SRM University)
  • 투고 : 2017.11.08
  • 심사 : 2017.12.25
  • 발행 : 2017.12.30
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초록

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. CXCR2 antagonist may reduce the neutrophil chemotaxis and alter the inflammatory response because the neutrophilic inflammation in the lung diseases is found to be largely regulated through CXCR2 receptor. Hence, in the present study, Topomer based Comparative Molecular Field Analysis (Topomer CoMFA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The best Topomer COMFA model was obtained with significant cross-validated correlation coefficient ($q^2$ = 0.487) and non cross-validated correlation coefficients ($r^2$ = 0.980). The model was evaluated with six external test compounds and its $r^2{_{pred}}$ was found to be 0.616. The steric and electrostatic contribution map show that presence of bulkier and electropositive group around cyclopropyl ring may contribute more for improving the biological activities of these compounds. The generated Topomer CoMFA model could be helpful for future design of novel and structurally related CXCR2 antagonists.

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참고문헌

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피인용 문헌

  1. Computational Analysis of Human Chemokine Receptor Type 6 vol.11, pp.2, 2017, https://doi.org/10.13160/ricns.2018.11.2.121