A new Cu(II)-O-Carvacrotinate complex: Synthesis, characterization and biological activity

Herein, we report the first example of the synthesis of a novel type of Cu(II) complex based on a natural product ligand derived from carvacrol. The copper(II) complex [Cu(DCA)₂(EtOH)]₂·2EtOH (1, HDCAO-carvacrotinic acid) has been synthesized and characterized by elemental analysis, IR spectroscopy, ESI-MS and single crystal X-ray analysis. Complex 1 and the carvacrotinic acid (2, HDCA) have been studied towards their antimicrobial and antiproliferative activities. For both compounds the antimicrobial activity was assessed against a panel of Gram-positive and Gram-negative bacteria and yeasts. The microdilution method allowed the determination of their Minimum Inhibitory Concentration (MIC) and minimum bactericidal concentration (MBC). Interestingly, both compounds seem to be more effective on yeasts rather than bacteria especially against C. albicans. Regarding the antimicrobial properties, the compounds appear to present a bacteriostatic behaviour, rather than bactericide. The antiproliferative effect of complex 1, O-carvacrotinic acid (HDCA) 2 and carvacrol (CA) 3 used as a reference to compare their antitumoral activity, was examined in 4 human tumor cell lines (ovarian carcinoma (A2780), colorectal carcinoma (HCT116), lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7)) and in normal human primary fibroblasts. Complex 1 exhibits a moderate cytotoxic activity against ovarian carcinoma cells (A2780), with no cytotoxicity in normal primary human fibroblasts. The moderate cytotoxicity observed in A2780 cells was due to an increase of cell apoptosis.