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

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.

Triazole analogues as potential pharmacological agents: a brief review

“…SAR studies revealed the presence of phenyl or alkyl substitution at N-4 has enhanced their antimicrobial activity towards strains of bacteria and fungi with MIC values of 8–16 μg/mL, where ciprofloxacin and fluconazole are the reference drugs (Table 1 ). Compounds 7a–7c were found to be the most potent antimicrobial agent [ 35 ]. …”

Novel 1,2,3-triazole-1,4-dihydropyridine-3,5-dicarbonitrile derivatives: synthesis and antibacterial evaluation

“…It was found as a lead inhibitor of bacterial DNA synthesis due to conformational fitting in the active site of targeted protein Thymidylate kinase (TMPK), which is an essential enzyme in bacterial DNA biosynthesis. 26 Among few fluorinated chalcone-triazole hybrids obtained from propargylated chalcones and organic azides, derivative with a 4-nitro group (MIC: 0.0032 μmol mL -1 ) was found to more potent than the standard Ciprofloxacin (MIC: 0.0047 μmol mL -1 ) against E. coli and S. epidermidis. While compound with -OMe functional group was also active against E. coli with MIC value of 0.0032 μmol mL -1 .…”

Untitled

“…Inhibition of the hERG gene has been strongly associated with prolonging QT syndrome, which often results in sudden heart attacks 54 . Molecular Docking: Anti-microbial agents (ligands) inhibit cell wall synthesis, nucleic acid synthesis, protein synthesis and metabolic pathways by binding to the specific proteins which are responsible for biological activities 55 . To understand the mechanism of anti-S. aureus activity of the identified ligands, a molecular docking study was carried out.…”