Effect of Gold(III) on Cytotoxicity and Antimicrobial Activity of Nifuroxazide Analogs

Metal ions can influence the biological activity of organic compounds, although the effects of metal addition depend on the chemical speciation of the resulting systems and their stability under biologically relevant conditions. Here, we investigated the interaction of gold(III) with nifuroxazide and eleven related hydrazones, as well as the effects of gold(III) addition on their cytotoxicity and antimicrobial activity. UV–Vis spectrophotometric titrations in dimethyl sulfoxide were analyzed using a proposed 1:2 metal-to-ligand equilibrium model, yielding conditional formation constants with log K′ values of approximately 8.8–9.1 under the experimental conditions. The proposed stoichiometry and structure of the gold-containing species remain to be confirmed by independent analytical methods. The addition of tetrachloroaurate(III) generally produced no substantial change in the cytotoxicity of the hydrazones toward HCT116 and HEK293T cells, although some compound-dependent effects were observed. In agar well diffusion assays, gold(III) addition increased the growth-inhibition zones against S. aureus for most hydrazones at the tested concentrations. Inhibition of P. aeruginosa and C. albicans was also observed in the presence of tetrachloroaurate(III), although the contribution of the gold-containing component and the nature of its interaction with the hydrazones require further investigation. These findings demonstrate that gold(III) addition can modify the observed biological activity of nifuroxazide analogs, while further studies are required to establish the chemical speciation under biological conditions and determine whether the enhanced antimicrobial effects represent genuine pharmacological synergy.