Interaction of VVO2-hydrazonates with lysozyme.

Abstract

Vanadium compounds (VCs) exhibit a broad range of pharmacological properties, with their most significant medical applications being in the treatment of cancer and diabetes. The therapeutic effects and mode of action of VCs may be associated with their ability to bind proteins and, consequently, understanding the VC-protein interaction is of paramount importance. Among the promising VCs, the V^VO₂ complex with the aroylhydrazone furan-2-carboxylic acid ((3-ethoxy-2-hydroxybenzylidene)hydrazide, hereafter denoted as VC1), deserves attention, since it exhibits cytotoxicity against various cancer cell lines, including HeLa. The interaction between VC1 and its analogue, denoted as VC2 (the dioxidovanadium(V) complex with (E)-N'-(1-(2-hydroxy-5-methoxyphenyl)ethylidene)furan-2-carbohydrazide), and hen egg white lysozyme (HEWL) was examined by UV-vis spectroscopy, fluorescence, circular dichroism, and X-ray crystallography. The interaction of VC1 and VC2 with HEWL does not alter the protein secondary and tertiary structure. Crystallographic studies indicate that the two metal complexes or V-containing fragments originating from VC1 and VC2 bind the protein via non-covalent interactions. Furthermore, when bound to HEWL, two VC1 molecules and two VC2 molecules form a supramolecular association stabilized by stacking interactions. This type of interaction could favour the binding of similar compounds to proteins and affect their biological activity.