Synthesis, in vitro, ADME Prediction, and Molecular Docking Studies of 1,3,4-Oxadiazole-piperazine Conjugates as New Anti-tubercular Agents

A series of 2-((5-((napthalen-2-yl-oxy)methyl)-1,3,4-oxadiazole-2-yl)thio)-1-(4-substituted piperazin-1-yl)ethan-1ones (3a-j) was synthesized by the reaction of 2-chloro-1(piperazin-1yl) ethan-1ones (1a-j) and 5-((naphthalen-2-yloxy) methyl)1,3,4-oxadiazole-2-thiol (2) in the presence of acetone and potassium carbonate. The in vitro antitubercular activity was performed through REMAassay against Mycobacterium smegmatis, which showed that compounds 3f and 3g had maximum activity, comparable to the standard drug isoniazid. The physiochemical properties and ADME descriptors were determined by using SwissADME online tools which established that synthesized molecules could be good leads as most of the descriptors (bioavailability, log P, Clearance, etc.) were found comparable to the reference molecules. The AutoDock (1.5.7) software was used for molecular docking studies and the result reinforced the conclusion of in vitro activity which was indicated by good interactions between synthesized ligands and the target protein i.e. InhA protein (PDB ID: 3FNG), in comparison with the standard drug Isoniazid.