Synthesis of 5-(Pyridin-4-yl)-oxadiazole Derivatives from Isoniazid and Evaluation of their Antimicrobial and Antitubercular Activities

Some new 5-(pyridin-4-yl)-1,3,4-oxadiazole derivatives were synthesized from isoniazid and evaluated for their antimicrobial and antitubercular activity. Isoniazid was treated with CS2 to obtain 5-(pyridin-4-yl)-1,3,4-oxadiazole-2-thiol (1), which was then hydrazinolyzed to obtain 2-hydrazinyl-5-(pyridin-4-yl)-1,3,4-oxadiazole (2). Cyclization of compound 2 afforded 6-(pyridin-4-yl)-[1,2,4]triazolo[3,4-b][1,3,4]oxadiazole (3) and 6-(pyridin-4-yl)-[1,3,4]oxadiazolo[3,2-d]tetrazole (4). Shciff’s bases (5 and 6) were synthesized by the reaction of compound 2 with furfuraldehyde and thiophene-2-aldehyde, respectively. Synthesized compounds were characterized using infrared (IR), 1H-nuclear magnetic resonance (NMR), 13C-NMR, and mass spectrometry. Antibacterial activity of all the compounds (1-6) was tested against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli bacterial species, and antifungal activity was tested against Candida albicans and Aspergillus niger fungal species and compared with reference drug amoxicillin for antibacterial activity and miconazole for antifungal activity. The antitubercular activity of the compounds 1-6 was tested against Mycobacterium tuberculosis H37Rv strain. Among all the compounds, compounds 2 and 6 displayed promising antibacterial, antifungal, and antitubercular activities and would be an effective candidate.