통합자연과학논문집 (Journal of Integrative Natural Science)

조선대학교 기초과학연구원 (The Basic Science Institute Chosun University)
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Comparative Molecular Field Analysis of Pyrrolopyrimidines as LRRK2 Kinase Inhibitors

  • Balupuri, Anand (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Balasubramanian, Pavithra K. (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Cho, Seung Joo (Department of Biomedical Sciences, College of Medicine, Chosun University)
  • 투고 : 2016.03.01
  • 심사 : 2016.03.25
  • 발행 : 2016.03.30
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초록

Leucine rich repeat kinase 2 (LRRK2) is a highly promising target for Parkinson's disease (PD) that affects millions of people worldwide. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of pyrrolopyrimidine-based selective LRRK2 kinase inhibitors. This study was performed to rationalize the structural requirements responsible for the inhibitory activity of these compounds. A reliable 3D-QSAR model was developed using comparative molecular field analysis (CoMFA) technique. The model produced statistically acceptable results with a cross-validated correlation coefficient ($q^2$) of 0.539 and a non-cross-validated correlation coefficient ($r^2$) of 0.871. Robustness of the model was further evaluated by bootstrapping and progressive scrambling analysis. This work could assist in designing more potent LRRK2 inhibitors.

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참고문헌

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피인용 문헌

  1. Molecular Docking Studies of p21-Activated Kinase-1 (PAK1) Inhibitors vol.9, pp.3, 2016, https://doi.org/10.13160/ricns.2016.9.3.161
  2. HQSAR Study on Substituted 1H-Pyrazolo[3,4-b]pyridines Derivatives as FGFR Kinase Antagonists vol.10, pp.2, 2016, https://doi.org/10.13160/ricns.2017.10.2.85