Abstract
Sunitinib is a potent anti-cancer scaffold that acts as a VEGFR-2 inhibitor. Although the scaffold exhibits potent anti-cancer activity, it is cardiotoxic and also induces hypothyroidism. The current research aims to optimize the Sunitinib for cardio-toxicity and thyro-toxicity by scaffold hopping approach using the admetSAR server. The server has optimized the physico-chemical properties of Sunitinib, which were contributing to the cardiotoxicity and thyro-toxicity. The library of the optimized compounds was further screened by the molecular docking studies and results were validated by the MD simulation and DFT analysis for VEGFR-2 inhibition. Compounds 163 and 432 exhibited the highest affinity to VEGFR-2 receptor with minimal cardiotoxicity and thyro-toxicity. These two compounds could be the starting point for the further discovery of angiogenic inhibitors.
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Authors are thankful to Principal, BVDU Poona College of Pharmacy, Pune and Principal, Vice Principal for conducting collaborative research work R. C. Patel Institute of Pharmaceutical Education and Research, authors are also thankful to Dr. Harun Patel, Division of Computer-Aided Drug Design for contributing for designing and carrying out research work at CADD division at R. C. Patel Institute of Pharmaceutical Education and Research.
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Chaudhari, B., Patel, H., Thakar, S. et al. Optimizing the Sunitinib for cardio-toxicity and thyro-toxicity by scaffold hopping approach. In Silico Pharmacol. 10, 10 (2022). https://doi.org/10.1007/s40203-022-00125-1
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DOI: https://doi.org/10.1007/s40203-022-00125-1