Synthesis, Antimycobacterial Screening and Molecular Docking Studies of 2-(Furan-3-yl)-5-phenyl-1,3,4-oxadiazole Derivatives

Microwave irradiation was used to efficiently synthesize certain 2-(furan-3-yl)-5-phenyl-1,3,4-oxadi-azole derivatives (3a-g), which were then tested against Mycobacterium tuberculosis using the Microplate Alamar Blue Assay (MABA) technique. Compounds 3a-g were synthesized by reacting furan-3-carboxylic acid (3-furoic acid) with ethanol to create furan-3-ethyl carboxylate (1), then hydrazinolysis was done with hydrazine hydrate to form furan-3-carbohydrazide (2). Finally, title compounds (3a-g) were produced by reacting compound 2 with a suitable aromatic acid in the presence of phosphorous oxychloride. Spectral data such as infrared (IR), proton nuclear magnetic resonance (¹H-NMR), and mass spectrometry were used to determine the structure of the final compounds. All compounds except 3b were identified as antitubercular leads having a MIC of 50 μg/mL against M. tuberculosis H37Rv, according to the results. The MIC value of compound 3b was determined to be 100 μg/mL. This can be improved further to find new antimycobacterial drugs. The results of docking studies clearly showed that all compounds fit nicely into the active site and formed hydrogen bonds, van der Waals, π-σ and π-alkyl interactions with the active site residues. The binding free energy of compounds 3a-g was found to be in the range of-7.0 to-9.2 kcal/ mol, indicating sufficient affinity between the oxadiazole analogue and the enzyme dihydrofolate reductase (DHFR).