Quinazoline clubbed thiazole and 1,3,4-oxadiazole heterocycles: synthesis, characterization, antibacterial evaluation, and molecular docking studies

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.

Graphical Abstract

Keywords:

• 1,3,4-oxadiazole
• antibacterial activity
• molecular docking
• quinazoline
• thiazole

Acknowledgments

The authors thank Schrödinger Inc. for providing Small-Molecule Drug Discovery Suite to perform the molecular docking studies. Authors are also thankful to Priyanka Desai, founder of iScribblers for the linguistic editing of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

One of the authors Prof. Nisheeth C. Desai is thankful to the University Grant Commission, New Delhi for awarding BSR Faculty-Fellowship 2019 (No. F 18-1/2011 (BSR)) and financial assistance. Authors are grateful to the UGC, New Delhi and Department of Science and Technology, New Delhi [grant no. DST-FIST-SR/FST/CSI-212/2010] for financial support under the NON-SAP and DST-FIST programs, respectively.