An integrated QSAR modeling approach to explore the structure-property and selectivity relationships of N-benzoyl-L-biphenylalanines as integrin antagonists

摘要

Integrins and are important targets to treat different inflammatory diseases, such as multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, atherosclerosis, and asthma. Despite being valuable targets, only a few work has been reported to date regarding molecular modeling studies on these integrins. Not only that, none of these reports addressed the selectivity issue between integrins and . Therefore, a major challenge regarding the design and discovery of selective integrin antagonists remains. In this study, a series of 142 N-benzoyl-l-biphenylalanines having both integrin and inhibitory activities were considered for a variety of QSAR approaches including regression and classification-based 2D-QSARs, Hologram QSARs, 3D-QSAR CoMFA and CoMSIA studies to identify the structural requirements of these integrin antagonists. All these QSAR models were statistically validated and subsequently correlated with each other to get a detailed understanding of the activity and selectivity profiles of these molecules.