Anti-Candida activity and cytotoxicity of a large library of new N-substituted-1,3-thiazolidin-4-one derivatives

On the basis of the recent findings about the biological properties of thiazolidinones and taking intoaccount the encouraging results about the antifungal activity of some (thiazol-2-yl)hydrazines, new Nsubstitutedheterocyclic derivatives were designed combining the thiazolidinone nucleus with thehydrazonic portion. In details, 1,3-thiazolidin-4-ones bearing (cyclo)aliphatic or (hetero)aromatic moietieslinked to the N1-hydrazine at C2 were synthesized and classified into three series according to thearomatic or bicyclic rings connected to the lactam nitrogen of the thiazolidinone. These molecules wereassayed for their anti-Candida effects in reference to the biological activity of the conventional topic(clotrimazole, miconazole, tioconazole) and systemic drugs (fluconazole, ketoconazole, amphotericin B).Finally, we investigated the selectivity against fungal cells by testing the compounds endowed with thebest MICs on Hep2 cells in order to assess their cell toxicity (CC50) and we noticed that two derivativeswere less cytotoxic than the reference drug clotrimazole. Moreover, a preliminary molecular modellingapproach has been performed against lanosterol 14-a demethylase (CYP51A1) to rationalize the activityof the tested compounds and to specify the target protein or enzyme.