Synthesis and in vitro antibacterial activity evaluation of coumarin-1,3,4-thiadiazoles hybrids

Purpose: Hybridization of two or more potent pharmacophores into a single molecule is one of the current strategies to synthesize compounds with improved pharmacological activity. Coumarin and 1,3,4-thiadiazole are scaffolds with potent antibacterial activity independently, and in this study, we synthesized coumarin-1,3,4-thiadiazole hybrid compounds and evaluated the in vitro antibacterial activity of the synthesized compounds. Methods: The two-step reaction, the Knoevangel condensation reaction followed by the nucleophilic addition reaction of Sciff bases, was conducted to synthesize nine pure compounds. The identity and purity of the compounds were characterized using FTIR and NMR spectroscopy. The in vitro antibacterial activity of the compounds was evaluated by determining their minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against four different bacterial strains. Results: A total of nine clear, yellowish crystals were synthesized. The physical and spectroscopic characteristics confirmed the purity and identity of the compounds. All the compounds showed good in vitro antibacterial activity. A compound that has –OH on the coumarin moiety and –CH¬3 on the 1,3,4-thiadiazole moiety showed a comparative MIC and MBC value with the control group (ciprofloxacin). Conclusion: Hybridization of the two scaffolds, coumarins and 1,3,4-thiadiazoles, showed significant antibacterial activity, and 4F was the compound with promising antibacterial activity that needs further development and evaluation.