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

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 & mu;g 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.

Automated summary

A series of analogs based on maslinic acid and oleanolic acid were designed and synthesized with potent antibacterial and antibiofilm activities. The conjugates were synthesized through a Cu-catalyzed cycloaddition reaction, resulting in new triazole derivatives. In vitro screening showed significant antibacterial activity against various strains, as well as moderate to significant antibiofilm activity. Molecular modeling revealed high antibacterial potentials for certain derivatives.