Molecular docking and antimalarial evaluation of hybrid -aminobenzoic acid 1,3,5 triazine derivatives inhibition of -DHFR.

In this study, a structurally guided pharmacophore hybridization strategy is used to combine the two key structural scaffolds, -aminobenzoic acid (PABA), and 1,3,5 triazine in search of new series of antimalarial agents. A combinatorial library of 100 compounds was prepared in five different series as [ (-), (-), (-), (-) and (-)] using different primary and secondary amines, from where 10 compounds were finally screened out through molecular property filter analysis and molecular docking study as promising PABA substituted 1,3,5-triazine scaffold as an antimalarial agent. The docking results showed that compounds and exhibited good binding interaction with Phe58, IIe164, Ser111, Arg122, Asp54 (-424.19 to -360.34 kcal/mol) and Arg122, Phe116, Ser111, Phe58 (-506.29 to -431.75 kcal/mol) against wild (1J3I) and quadruple mutant (1J3K) type of -DHFR. These compounds were synthesized by conventional as well as microwave-assisted synthesis and characterized by different spectroscopic methods. antimalarial activity results indicated that two compounds and showed promising antimalarial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains of with IC (1.24-4.77 μg mL) and (2.11-3.60 μg mL). These hybrid PABA substituted 1,3,5-triazine derivatives might be used in the lead discovery towards a new class of -DHFR inhibitors.Communicated by Ramaswamy H. Sarma.