Abstract
Platelet-derived growth factor (PDGF) is one of the various growth factors, which involves in regulation of cell growth and division. In this work, 3D-quantitative structure–activity relationship studies of 75 quinazolines derivative as PDGFR’s inhibitor were performed. Based on the cognate ligand (PBD code: 3MJG 2.3 Å), numerous alignment methods were used to obtain reliable comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA) models. Docked pose of the most active compound followed by database alignment led to derived best CoMFA model (q 2 = 0.531, r 2ncv = 0.913). With the same alignment, a statistically reliable CoMSIA model with all the five fields was also derived (q 2 = 0.525, r 2ncv = 0.889). A test set was used to validate both the models, which gave satisfactory predictive (r 2pred ) values of 0.77 and 0.79, respectively. Contour maps of CoMFA and CoMSIA revealed the effect of important structural features on biological activity within the binding pocket and explained its interactions with ligand.
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Acknowledgments
Authors are highly acknowledged Higher Education Commission (HEC) of Pakistan for their financial support, and also grateful to Prof. Bernd M. Rode (University of Innsbruck) for providing their technical and software support to conduct this research work.
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Ul-Haq, Z., Zafar, S.K., Khan, N. et al. Structure-based 3D-QSAR studies on quinazoline derivatives as platelets-derived growth factor (PDGFR) inhibitors. Med Chem Res 23, 4070–4084 (2014). https://doi.org/10.1007/s00044-014-0946-8
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DOI: https://doi.org/10.1007/s00044-014-0946-8