Leishmaniasis is a neglected parasitic disease caused by various Leishmania species. The discovery of new protozoa drugs makes it easier to treat the disease; but, conventional clinical issues like drug resistance, cumulative toxicity, and target selectivity are also getting attention. So, there is always a need for new therapeutics to treat Leishmaniasis. Here, we have reported 2,3-dihydroquinazolin-4(1H)-one derivative as a new class of anti-leishmanial agents. Two derivatives, 3a (6,8-dinitro-2,2-disubstituted-2,3-dihydroquinazolin-4(1H)-ones) and 3b (2-(4-chloro-3-nitro-phenyl)-2-methyl-6,8-dinitro-2,3-dihydro-1H-quinazolin-4-one) were prepared that show promising in silico anti-leishmanial activities. Molecular docking was performed against the Leishmanial key proteins including Pyridoxal Kinase and Trypanothione Reductase. The stability of the ligand-protein complexes was further studied by 100 ns MD simulations and MM/PBSA calculations for both compounds. 3b has been shown to be a better anti-leishmanial candidate. In vitro studies also agree with the in-silico results where IC50 for 3a and 3b was 1.61 and 0.05 µg/mL, respectively.
