Synthesis, antibacterial activity and molecular docking study of vanillin derived 1,4-disubstituted 1,2,3-triazoles as inhibitors of bacterial DNA synthesis

Mumtaz Hussain; Tahir Qadri; Zahid Hussain; Aamer Saeed; Pervaiz Ali Channar; Syeda Aaliya Shehzadi; Mubashir Hassan; Fayaz Ali Larik; Tarique Mahmood; Arif Malik

doi:10.1016/j.heliyon.2019.e02812

Synthesis, antibacterial activity and molecular docking study of vanillin derived 1,4-disubstituted 1,2,3-triazoles as inhibitors of bacterial DNA synthesis

Heliyon. 2019 Nov 19;5(11):e02812. doi: 10.1016/j.heliyon.2019.e02812. eCollection 2019 Nov.

Authors

Affiliations

¹ Department of Chemistry, University of Karachi, 75270, Karachi, Pakistan.
² Department of Chemistry, Quaid-i-Azam University, 45320, Islamabad, Pakistan.
³ Sulaiman Bin Abdullah Aba Al-Khail-Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS), International Islamic University, 44000, Islamabad, Pakistan.
⁴ Institute of Molecular Biology and Biotechnology, The University of Lahore, Defence Road Campus, Lahore, Pakistan.

Abstract

Antimicrobial resistance (AMR) compelled scientists in general while pharmacists, chemists and biologists in specific to believe that we could always remain ahead of the pathogens. The pipeline of new drugs is running gasping and the inducements to develop new antimicrobials to address the global problems of drug resistance are weak. In this pursuit, effective endeavours to prepare new anti-bacterial entities is highly wished. The present study demonstrates successful synthesis of a library of 1,4-disbustituted 1,2,3-triazoles (3a-3k) using Click-chemistry concept and anti-their bacterial potential. In this 1,3-dipolar cycloaddition, the 3-methoxy-4-(prop-2-yn-1-yloxy)benzaldehyde (1) was used as alkyne partner which was synthesized from vanillin and propargyl bromide and further reacted with differently substituted arylpropoxy azides (2a-k) to furnish series of mono and bis1,4-disubstituted-1,2,3-triazoles. All the synthesized compounds were characterized spectroscopically and were evaluated for their initial antimicrobial activity. Preliminary results of antibacterial screening revealed that the synthesized compounds have the highest inhibitory effects compare to the control ciprofloxacin. The compounds 3b and 3g were found to be the most active (MIC: 5 μg/mL, MIC: 10 μg/mL respectively) against various strains of gram-positive and gram-negative bacteria. The molecular docking study against 4GQQ protein with synthesized ligands was performed to see the necessary interactions responsible for anti-bacterial activity. The docking analysis of the most potent compound 3g supported the antibacterial activity exhibiting high inhibition constant and binding energy.

Keywords: 1,4-Disubstituted 1,2,3-triazoles; Antibacterial agents; Click chemistry; Molecular docking; Organic chemistry; Pharmaceutical chemistry; Thymidylate kinase (TMPK) inhibitors.