Synthesis, Biological Properties, and Molecular Docking Study of Novel 1,2,3-Triazole-8-quinolinol Hybrids.

A new series of 1,2,3-triazole-8-quinolinol hybrids were synthesized in good yields using monosubstituted acetonitriles and 5-azidomethyl-8-quinolinol as the starting reagents via a one-step protocol. The structures of 1,2,3-triazole-8-quinolinol hybrids were characterized by nuclear magnetic resonance ( 1 H and 13 C NMR) spectroscopy and elemental analysis. Antibacterial activity in vitro of all the synthesized hybrids was investigated against Escherichia coli ( E. coli ), Xanthomonas fragariae ( X. fragariae ), Staphylococcus aureus ( S. aureus ), and Bacillus subtilis ( B. subtilis ) applying the methods of disk diffusion and minimal inhibition concentration (MIC). Hybrid 7 exhibited excellent antibacterial capacity, with an MIC value of 10 μg/mL against S. aureus and 20 μg/mL against B. subtilis , E. coli , and X. fragariae , which were comparable to those that of the standard antibiotic nitroxoline. A structure-activity relationship (SAR) study of 1,2,3-triazole-8-quinolinol hybrids showed that introducing electron-donating substituents in the 1,2,3-triazole ring at the 4-position is important for activity. Quantum chemical calculations have been undertaken to employ the Gaussian software in the B3LYP, HF, and M062X basis sets using 3-21g, 6-31g, and SDD levels to further explain linkages within the antibacterial findings. Furthermore, molecular docking investigations were also conducted to investigate the binding affinities as well as the interactions of some hybrids with the target proteins. An absorption, distribution, metabolism, excretion, and toxicity (ADME/T) investigation was carried out to scrutinize the viability of employing the 1,2,3-triazole-8-quinolinol hybrids as medicines.