Affiliation:
1. L. M. College of Pharmacy Navrangpura, Ahmedabad Gujarat 380 009 India
2. Department of Chemistry School of Sciences National Institute of Technology Andhra Pradesh Tadepalligudem, Andhra Pradesh 534101 India
3. Department of Pharmaceutical Chemistry Institute of Pharmacy Nirma University Ahmedabad, Gujarat 382 481 India
Abstract
AbstractMalaria is the most severe and common parasitic infection, with P. falciparum responsible for the majority of cases and deaths each year. As anti‐malarial drug resistance continues to increase, novel compounds with anti‐ P. falciparum activity must be identified. In search of a new molecule to cure the resistant malarial parasite, a total of 1,70,269 ligands from the Asinex BioDesign library 2021.2 were virtually screened using AutoDock Vina against wild‐type P. falciparum dihydrofolate reductase‐thymidylate synthase (PfDHFR‐TS). The computational molecular modeling investigations indicated the discovery of seventeen new compounds (2‐18) with higher binding energy compared to the PfDHFR‐TS inhibitor, pyrimethamine (1). Furthermore, the study employing drug‐likeness criteria and their ADMET profile suggested that these hits were the most promising drug candidates due to higher absorption and druggability. Furthermore, GROMACS 2023.4 was used to perform the molecular dynamics simulations on the foremost compound (2) having sufficient stability, leading to a key step towards the search of novel PfDHFR‐TS inhibitors against malaria.