Title:Synthesis and Evaluation of Imidazole Derivatives Bearing Imidazo[2,1-b] [1,3,4]thiadiazole Moiety as Antibacterial Agents
Volume: 20
Issue: 1
Author(s): Wen-Bo Xu, Siqi Li, Chang-Ji Zheng, Yu-Xuan Yang, Changhao Zhang and Cheng-Hua Jin*
Affiliation:
- Interdisciplinary Program of Biological Function Molecules, College of Integration Science, Yanbian University, Yanji
133002, P.R. China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, P.R. China
Keywords:
Imidazole, thiadiazole, pyridine, antibacterial, hemolysis, cytotoxicity.
Abstract:
Background: Drug-resistant infections kill hundreds of thousands of people globally
every year. In previous work, we found that tri-methoxy- and pyridine-substituted imidazoles show
strong antibacterial activities.
Objective: The aim of this work was to investigate the antibacterial activities and bacterial resistances
of imidazoles bearing an aromatic heterocyclic, alkoxy, or polycyclic moiety on the central
ring.
Methods: Three series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4-
yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (13a-e, 14a-d, and 15a-f) were synthesized and their
antibacterial activity was evaluated. The structures were confirmed by their 1H NMR, 13C NMR,
and HRMS spectra. All the synthesized compounds were screened against Gram-positive, Gramnegative,
and multidrug-resistant bacterial strains.
Results: More than half of the compounds showed moderate or strong antibacterial activity. Among
them, compound 13e (MICs = 1-4 μg/mL) showed the strongest activity against Gram-positive and
drug-resistant bacteria as well as high selectivity against Gram-negative bacteria. Furthermore, it
showed no cytotoxicity against HepG2 cells, even at 100 μM, and no hemolysis at 20 μM.
Conclusion: These results indicate that compound 13e is excellent candicate for further study as a
potential antibacterial agent.