Pharmacokinetic predictions and docking studies of substituted aryl amine-based triazolopyrimidine designed inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH)

Abstract

Abstract Background The sixteen (16) designed data set of substituted aryl amine-based triazolopyrimidine were docked against Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) employing Molegro Virtual Docker (MVD) software and their pharmacokinetic property determined through SwissADME predictor. Results The docking studies shows compound D16, 5-((6-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)amino)benzo[b]thiophen-4-ol to be the most interactive and stable derivative (re-rank score = − 114.205 kcal/mol) resulting from the hydrophobic as well as hydrogen interactions. The hydrogen interaction produced one hydrogen bond with the active residues LEU359 (H∙∙H∙∙O) at a bond distances of 2.2874 Å. All the designed derivatives were found to pass the Lipinski rule of five tests, supporting the drug-likeliness of the designed compounds. Conclusion The ADME analysis revealed a perfect concurrence with the Lipinski Ro5, where the derivatives were found to possess good pharmacokinetic properties such as molar refractivity (MR), number of rotatable bonds (nRotb), log of skin permeability (log Kp), blood-brain barrier (BBB). These results could a deciding factor for the optimization of novel antimalarial compounds.