Molecular Docking, ADMET Prediction, and Quantum Computational on 2-Methoxy Benzoyl Hydrazone Compounds as Potential Antileishmanial Inhibitors

Abstract

Leishmaniasis is a neglected disease that affects about one million people a year worldwide and is present in over 90 countries. This illness is a serious public health issue since it can result in mutilation, incapacity, and even death. The drugs currently used for treatment are highly toxic, ineffective, expensive, and may cause antiparasitic resistance. A series of twenty-five 2-methoxy benzoyl hydrazone derivatives have recently been identified as promising antileishmanial inhibitors and was addressed using a molecular docking approach. All docked compounds interacted well within the active pocket of the receptor. Compounds M12, M15, M16, and M20 show a good binding energy value of -9.40, -8.90, -9.00, and -9.20 Kcal/mol, respectively, compared to pentamidine (-8.20 Kcal/mol), used as reference drug. These molecules also present many types and numbers of interactions with the studied receptor. The studied molecules were evaluated for their pharmacokinetic properties using ADMET prediction. They showed good bioavailability, particularly the molecules M12, M15, and M16 which were found to be non-toxic. Quantum calculations using the DFT approach were performed on the four selected compounds to determine the most electrophilic and nucleophilic of them. These findings would be very helpful in the search for new antileishmanial inhibitors.