Enhanced efficacy of a Cu2+ complex of curcumin against Gram-positive and Gram-negative bacteria: Attributes of complex formation

Curcumin is a tantalizing molecule with multifaceted therapeutic potentials. However, its therapeutic applications are severely hampered because of poor bioavailability, attributed to its instability and aqueous insolubility. In an attempt to overcome this inherent limitation and develop curcumin-based antibacterials, we had earlier synthesized and characterized a metal complex of Cu(II) with curcumin, having the formula [Cu(Curcumin)(OCOCH3)(H2O)], hereafter referred to as Cu(Cur). In this study, the complex, i.e., Cu(Cur), was investigated for its stability and antibacterial activity along with its possible mechanism of action in comparison to the parent molecule, curcumin. Complex formation resulted in improved stability as Cu(Cur) was found to be highly stable under different physiological conditions. Such improved stability was verified with the help of UV–Vis spectroscopy and HPLC. With improved stability, Cu(Cur) exhibited potent and significantly enhanced activity over curcumin against both E. coli and S. aureus. Calcein leakage assay revealed that the complex triggered immediate membrane permeabilization in S. aureus. This membrane disruptive mode of action was further corroborated by microscopic visualization. The excellent potency of the complex was augmented by its safe toxicological profile as it was non-hemolytic and non-cytotoxic towards mammalian cells, making it a suitable candidate for in vivo investigations. Altogether, this investigation is a critical appraisal that advocates the antibacterial potential of this stable, membrane-targeting and non-toxic complex, thereby presenting new perspectives for its therapeutic application against bacterial infections.