Synthesis, antimicrobial evaluation and QSAR analysis of novel nalidixic acid based 1,2,4-triazole derivatives

Novel nalidixic acid based 1,2,4-triazole derivatives were synthesized and characterized using spectral techniques like 1H NMR, 13C NMR, IR and mass spectrometry. All these compounds were screened for antimicrobial activity against five bacteria and two pathogenic fungi. Most of these compounds showed better antimicrobial activity than the parent compound, 4-amino-5-mercapto-1,2,4-triazole. Among all the screened compounds, 3-{6-(2-chlorophenyl)-1,2,4-triazolo [3,4-b] [1,3,4]thiadiazol-3-yl}-1-ethyl-7-methyl-1,8-naphthyridin-4(1H)-one (23) was emerged as promising antimicrobial agent (MIC = 16 μg/mL). Quantitative structure activity relationship (QSAR) analysis was carried out using various distance-based topological indices, steric and hydrophobic parameters. Based on the QSAR analysis it is indicative that lipophilic and steric parameters are the pre-requisites for these molecules to act as potent antimicrobial agents.

Graphical abstractSynthesis and antimicrobial evaluation of novel nalidixic acid based 1,2,4-triazole derivatives were described. Their 2D quantitative structure activity relationship QSAR) analysis has been carried out.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel 33 nalidixic acid based 1,2,4-triazole derivatives were synthesized. ► Bioassay against 7 pathogens revealed compound 5 as best antimicrobial agent. ► QSAR models showed significance of hydrophobic parameter for antimicrobial activity.