Antifungal activity of silver and zinc complexes of sulfadrug derivatives incorporating arylsulfonylureido moieties.

Two well known antimicrobial sulfonamides, sulfadiazine and sulfamerazine were reacted with arylsulfonyl isocyanates, affording several new arylsulfonylureido derivatives. These compounds were subsequently used as ligands (in the form of conjugate bases, as sulfonamide anions) for the preparation of metal complexes containing silver and zinc. The newly synthesized complexes, unlike the free ligands, proved to act as effective antifungal agents against several Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 1.5-5 microg/ml. The mechanism of antifungal action of these complexes seems to be different from that of the azole antifungals acting as lanosterol-14-alpha-demethylase inhibitors. Levels of sterols assayed in the fungi cultures treated with these new antifungals were equal in the absence or in the presence of the tested compounds. This is in strong contrast with similar experiments in which ketoconazole has been used as antifungal, when drastically reduced ergosterol amounts could be detected. Thus, it is probable that the inhibition of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls, imparts antifungal activity to the new metal complexes reported here.