Design, Synthesis and Antibacterial Activity of Coumarin-1,2,3-triazole Hybrids Obtained from Natural Furocoumarin Peucedanin

Abstract

Synthesis of 1,2,3-triazole-substituted coumarins and also 1,2,3-triazolyl or 1,2,3-triazolylalk-1-inyl-linked coumarin-2,3-furocoumarin hybrids was performed by employing the cross-coupling and copper catalyzed azide-alkyne cycloaddition reaction approaches. The synthesized compounds were evaluated for their in vitro antibacterial activity against <i>Staphylococcus</i> <i>aureus</i>, <i>Bacillius</i> <i>subtilis</i>, <i>Actinomyces</i> <i>viscosus</i> and <i>Escherichia</i> <i>coli</i> bacterial strains. Coumarin-benzoic acid hybrids <b>4с</b>, <b>42с</b> and 3-((4-acetylamino-3-(methoxycarbonyl)phenyl)ethynyl)coumarin (<b>29</b>) showed promising activity against <i>S</i>. <i>aureus</i> strains, and the 1,2,3-triazolyloct-1-inyl linked coumarin-2,3-furocoumarin hybrid <b>37c</b> was endowed with high selectivity against <i>B. subtilis</i> and <i>E. coli</i> species. The in vitro antibacterial activity of <b>4с</b>, <b>29</b>, <b>37c</b> and <b>42с</b> can potentially be compared with that of a number of modern antibiotic drugs used in the clinic, suggesting promising prospects for further research. A detailed study of the molecular interactions with the targeted protein MurB was performed using docking simulations and the obtained results are quite promising.