A series of imidazothiazole and oxazolopyridine derivatives as human silent information
regulator (SIRT1) activators was subjected to the integrated 2D and 3D QSAR approaches. The derived
3D QSAR models yielded high cross-validated q2 values of 0.682 and 0.628 for CoMFA and CoMSIA,
respectively. The non-cross validated values of r2
= 0.89; predictive r2
test = 0.69 for CoMFA and
r2=0.87; predictive r2
test =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. The developed 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.
Keywords: SIRT1 activators, imidazothiazole and oxazolopyridine derivatives, 3D QSAR, 2D QSAR, CoMFA and CoMSIA.
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