Design, Molecular Docking and ADMET Studies of 2-Substituted-5-[ (1H-benzimidazol-2yl) methyl] 1,3,4-Oxadiazole Derivatives as Pteridine Reductase 1 Inhibitors.

PHADKE, SHRADDHA A.; SOMANI, RAKESH R.; PATHAK, DEVENDER

With a view to develop effective agents against Leishmniasis, 2-substituted-5-[(1H-benzimidazol-2yl) methyl]1,3,4-oxadiazole derivatives (OX1-OX12) were designed. The series was designed by targeting Pteridine reductase 1 which is an important enzyme responsible for folate ad pterin metabolism. In silico studies to understand binding of compounds with enzyme as well as physicochemical properties were undertaken. Compounds OX5 and OX8 gave the best docking scores of -64.7777 and -60.4161 respectively that were close to dihyrobiopterine (original substrate). The docking scores indicated that enzyme binding may be governed by the nature and size of the substituents on the oxadiazole ring. Bioactivity studies suggested the possible drug mechanism as enzyme inhibition. All the compounds complied with Lipinski's rule of five. Most of the compounds displayed favorable ADMET properties.

MOLECULAR docking; PTERIDINES; OXADIAZOLES; LEISHMANIASIS; BENZIMIDAZOLE derivatives

International Journal of Pharmaceutical Research (09752366), 2021, Vol 13, Issue 2, p2205

0975-2366

Academic Journal

10.31838/ijpr/2021.13.02.309