Novel Quinazolin-2,4-Dione Hybrid Molecules as Possible Inhibitors Against Malaria: Synthesis andin silicoMolecular Docking Studies

The research explores the synthesis of a series of novel hybrid quinazolin-2,4-dione analogs bearing acetyl/amide bridged-nitrogen heterocyclic moieties such as azetidinone, pyrrole, oxazole, oxadiazole, thiazole, pyrazole, and thiazolidine scaffolds2-16. The newly synthesized compounds were structurally confirmed by means of IR,H-1-NMR,C-13-NMR, MS and elemental analysis. In addition, anin silicomolecular docking analysis of new compounds and standard drug (Chloroquine) has been performed to analyze the binding modes of interaction to the putative active site ofPlasmodium falciparumDihydroorotate dehydrogenase (pfDHODH). Aiming to search for potentially better antimalarials, a modern approach has been undertaken to identify new quinazolin-2,4-dione derivatives targetingpfDHODH. The identification of antimalarial activity of the newly synthesized compounds by using experimental techniques is expensive and requires extensive pains and labor. The compound11showed the highest binding affinity againstpfDHODH. Moreover, the electrostatic potential (ESP) of the docked molecules was also calculated. Further, the pharmacokinetic properties (ADMET) of the prepared compounds were predicted throughin silicotechnique.