Design, semi-synthesis and molecular docking of new antibacterial and antibiofilm triazole conjugates from hydroxy-triterpene acids and fluoroquinolones

Abstract

A series of maslinic acid (MA) and oleanolic acid (OA)-based analogs with potent antibacterial and antibiofilm activities were designed and semi-synthesized starting from isolated pentacyclic triterpene acids as natural products from olive pomace (Olea europaea L.). These conjugates were synthesized via a last step of Cu-catalyzed azide–alkyne cycloaddition (CuAAC) between propargylated quinolone/fluoroquinolones (QN/FQNs) and MA/OA azides to achieve new triazole derivatives in overall excellent yields. The latter hybrids were screened in vitro for their antibacterial and antibiofilm activities towards two Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Results indicated that some of the maslinic acid derivatives exhibited significant activity against all tested strains with MIC values within a range of 3.25–30 μg mL⁻¹. Moreover, evaluated compounds depicted moderate to significant antibiofilm activity with inhibition percentage going up to 68.75% against S. aureus biofilm formation. The molecular modeling using docking study of the antibacterial activity of synthesized compounds showed that some derivatives displayed high antibacterial potentials.