Synthesis and Antimicrobial Evaluation of 1H-1,2,3-Triazole-Linked Quinoline-Phenolic Natural Product Conjugates.

AbstractA new library of quinoline–natural product conjugates bearing 1,2,3-triazole moiety as a linker has been synthesized using the copper(I) catalyzed azide-alkyne [3 + 2] cycloaddition reaction (CuAAC) methodology. The structure characterization of the synthesized compounds was achieved using NMR and HRMS analysis. The compounds were subsequently screened for their antimicrobial efficacies against methicillin resistant <italic>Staphylococcus aureus</italic> (MRSA), MDR <italic>Klebsiella pneumoniae</italic>, <italic>Acinetobacter baumannii</italic>, <italic>Pseudomonas aeruginosa</italic>, <italic>Escherichia coli, Candida albicans,</italic> and <italic>Cryptococcus neoformans</italic>. The studied compounds generally displayed stronger inhibition of microbial cell growth compared to their parent phenolic natural products. Eugenol, thymol, guaiacol, and <italic>o</italic>-vanillin based 1<italic>H</italic>-1,2,3-triazole compounds exhibited the best antimicrobial profiles while the pathogen, <italic>A. baumannii</italic> showed the highest susceptibility to the hybrids. Precisely, hybrids <bold>19a</bold>, <bold>20b</bold>, and <bold>25b</bold> derived from eugenol, thymol, and <italic>o</italic>-vanillin, respectively, exhibited over 50% growth inhibition of the pathogen. <italic>K. pneumoniae</italic> was however strongly resistant to the compound series. <italic>In silico</italic> docking studies of the representative compounds further explored the characteristic binding orientations of these compounds in the active sites of the bacterial and fungal proteins. Overall, we perceive that rational scaffold hopping of these compounds holds promise to offer novel antimicrobial agents with enhanced potency. [ABSTRACT FROM AUTHOR]