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

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Abstract

Integrins \({\upalpha }_{4}{\upbeta }_{7}\) and \({\upalpha }_{4}{\upbeta }_{1}\) 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 \({\upalpha }_{4}{\upbeta }_{7}\) and \({\upalpha }_{4}{\upbeta }_{1}\). 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 \({\upalpha }_{4}{\upbeta }_{7}\) and \({\upalpha }_{4}{\upbeta }_{1}\) 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.

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Acknowledgements

NA is grateful to University Grants Commission (UGC), New Delhi, India, for providing Rajiv Gandhi National Fellowship (Grant No. F1-17.1/2014-15/RGNF-2014-15-SC-WES-73725/SA-III/Website). SG thanks to the UGC, New Delhi, India, for awarding UGC-Start up Grant (No. F.30-106/2015-BSR). Authors are thankful to the authority of Jadavpur University, India, and Dr. Harisingh Gour University, India, for providing research facilities.

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  1. Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box 17020, Kolkata, West Bengal, 700032, India

    Sk. Abdul Amin, Nilanjan Adhikari & Tarun Jha

  2. Laboratory of Drug Design and Discovery, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar, Madhya Pradesh, 470003, India

    Sonam Bhargava & Shovanlal Gayen

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Amin, S.A., Adhikari, N., Bhargava, S. et al. An integrated QSAR modeling approach to explore the structure–property and selectivity relationships of N-benzoyl-l-biphenylalanines as integrin antagonists. Mol Divers 22, 129–158 (2018). https://doi.org/10.1007/s11030-017-9789-9

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