Quinazoline clubbed thiazole and 1,3,4-oxadiazole heterocycles: synthesis, characterization, antibacterial evaluation, and molecular docking studies
Nisheeth C. Desai, Niraj Shihory, Ashvinkumar G. Khasiya, Unnat Pandit, Vijay M. Khedkar
Abstract
In search of potent antibacterial agents, a series of novel quinazolines, bearing thiazole and 1,3,4-oxadiazole heterocycles 6a–j (3-(4-methyl-5-(4-((arylamino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)thiazol-2-yl)-2-phenylquinazolin-4(3H)-ones) were synthesized and the structures of the compounds were elucidated by standard spectroscopic techniques. In order to evaluate their antibacterial potential, the antibacterial assay of synthesized compounds 6a–j was performed against MTCC strains, wherein compounds 6d (3-(4-methyl-5-(4-(((4-nitrophenyl)amino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)thiazol-2-yl)-2-phenylquinazolin-4(3H)-one) (Escherichia coli, MIC = 100 µg mL−1) and 6e (3-(5-(4-(((2-chlorophenyl)amino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-methylthiazol-2-yl)-2-phenylquinazolin-4(3H)-one) (E. coli, MIC = 62.5 µg mL−1) were most active against Gram-negative bacteria while compound 6f (3-(5-(4-(((4-chlorophenyl)amino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-methylthiazol-2-yl)-2-phenylquinazolin-4(3H)-one) (Staphylococcus aureus, MIC = 50 µg mL−1) was most active against Gram-positive bacteria. Furthermore, molecular docking simulation was performed to determine the probable binding mode and affinity of the synthesized compounds toward bacterial DNA gyrase. The preliminary results pave the way for further designing the thiazole based 1,3,4-oxadiazoles heterocycles for enhancing their potency as antibacterial agents.