SYNTHESIS, STRUCTURAL CHARACTERIZATION AND ANTIBACTERIAL POTENTIAL OF NEW IBUPROFEN-BASED 1,3,4–OXADIAZOLE– THIOACETAMIDE HYBRIDS

Abstract

A new series of 1,3,4-oxadiazole–thioacetamide hybrids (7a–7j) based on ibuprofen was synthesized (61–78% yields) and tested for antibacterial activity in order to address multidrug resistance (MDR). Ibuprofen was converted into ethyl 2-(4-isobutylphenyl) propanoate (2) in the multi-step synthesis process, which was then hydrazinolyzed to produce 2-(4-isobutylphenyl) propanohydrazide (3). The primary building block, 5-(1-(4-isobutylphenyl)ethyl)-1,3,4-oxadiazole-2-thiol (4), was produced via base-catalyzed cyclization of 3 with carbon disulfide. Target hybrids (7a–7j) were successfully produced by nucleophilically substituting 4 with different N-substituted aryl acetamides (6a–j) in the presence of lithium hydride (LiH). Melting point tracking and high-resolution FT-IR spectrum analysis (4000–400  cm⁻¹  range) were used to evaluate structural frameworks. In vitro screening against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) strains using the agar well diffusion method showed that hybridization introduces remarkable antibacterial characteristics in comparison to the fully inactive parent ibuprofen (0.0 mm). Higher susceptibility was shown by Gram-positive bacteria, and the most effective candidate in the entire collection was the 4-nitro-substituted hybrid (7j).