Integrated Ligand and Structure-Based Investigation of Structural Requirements for Silent Information Regulator 1 (SIRT1) Activation
- 주제(키워드) SIRT1 activators , Imidazothiazole and oxazolopyridine derivatives , 3D QSAR , 2D QSAR , CoMFA , CoMSIA
- 주제(기타) Chemistry, Medicinal
- 설명문(일반) [Choi, Sun] Ewha Womans Univ, Coll Pharm, Natl Leading Res Lab Mol Modeling & Drug Design, Seoul 03760, South Korea; [Choi, Sun] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Choi, Sun] Ewha Womans Univ, Global Top Res Program 5, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 BENTHAM SCIENCE PUBL LTD
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000160043
- 본문언어 영어
- Published As http://dx.doi.org/10.2174/1568026619666181220111059
초록/요약
A series of imidazothiazole and oxazolopyridine derivatives as human Silent Information Regulator 1 (SIRT1) activators were subjected to the integrated 2D and 3D QSAR approaches. The derived 3D QSAR models yielded high cross-validated q(2) values of 0.682 and 0.628 for CoMFA and CoMSIA, respectively. The non-cross validated values of r(training)(2) = 0.89; predictive r(test)(2) = 0.69 for CoMFA and r(2) -0.87; predictive r(test)(2) -0.67 for CoMSIA reflected the statistical significance of the developed model. The steric, electrostatic, hydrophobic and hydrogen bond acceptor interactions have been found important in describing the variation in human SIRT1 activation. Further, 2D QSAR model for the same dataset yielded high statistical significance and derived 2D model's parameters corroborated with the 3D model in terms of features. Derived model was also validated by the crystal structure of active conformation of SIRT1. Developed models may be useful for the identification of potential novel human SIRT1 activators as a therapeutic agent.
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