In-Silico Drug Design And Adme Studies Of Substituted 1, 3, 4-Oxadiazole Analogues As Potent Mycobacterial Dpre1 Enzyme Inhibitors

Abstract

Mycobacterial infections and multidrug-resistant (MDR) strains of Mycobacterium generate high mortality, this has triggered the scientific community to search for novel, effective, and safer therapeutics. A series of 4, 5-disubstituted-1, 3, 4-oxadiazole derivatives were screened for mycobacterial activity against H37Rv, MDR and XDR strains. To recognize the mechanism of action of these compounds and to identify their supposed drug target, molecular docking and dynamics studies were employed against DprE1 mycobacterial enzyme, which is reported to be an essential enzyme for mycobacterial growth and survival. The ADME and drug-likeness properties revealed that all the compounds have good pharmacokinetic properties. All the compounds have high affinity towards the enzyme. The newly synthesized derivatives were confirmed through FT-IR, 1 H-NMR, and LCMS. In-vitro microplate alamar blue assay (MABA) to determine the MIC (minimum inhibitory concentration) values against Mycobacterium tuberculosis H37Rv was performed for the synthesized compounds. The synthesized compounds 2A, 3A, 4A, 5A and 6A exhibited promising activity against Mycobacterium tuberculosis.