Optimizing the Sunitinib for cardio-toxicity and thyro-toxicity by scaffold hopping approach

Bhagyashri Chaudhari; Harun Patel; Snehal Thakar; Iqrar Ahmad; Deepali Bansode

doi:10.1007/s40203-022-00125-1

Optimizing the Sunitinib for cardio-toxicity and thyro-toxicity by scaffold hopping approach

In Silico Pharmacol. 2022 Jul 2;10(1):10. doi: 10.1007/s40203-022-00125-1. eCollection 2022.

Authors

Bhagyashri Chaudhari¹, Harun Patel², Snehal Thakar¹, Iqrar Ahmad², Deepali Bansode¹

Affiliations

¹ Department of Pharmaceutical Chemistry, Bharati Vidyapeeth (Deemed to be), Poona College of Pharmacy, Erandwane, Kothrud, Pune, 411038 India.
² Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, 425405 India.

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.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-022-00125-1.

Keywords: Cardiotoxicity; Docking; Sunitinib; Thyro-toxicity; VEGFR-2.