Antifungal activity of Ag(I) and Zn(II) complexes of aminobenzolamide (5-sulfanilylamido-1,3,4-thiadiazole-2-sulfonamide) derivatives

Aminobenzolamide (5-sulfanilylamido-1,3,4-thiadiazole-2-sulfonamide) is a p otent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), bei ng at the same time structurally similar to the antimicrobial sulfonamides. Here we report that the reaction of aminobenzolamide with arylsulfonyl iso cyanates affords a series of new arylsulfonylureido derivatives which were subsequently used as ligands tin the form of conjugate bases, as sulfonamid e anions) for the preparation of metal complexes containing Ag(I) and Zn(II ). All the new compounds proved to be very potent inhibitors of CA (isozyme s I, II and IV). The newly synthesized complexes, unlike the free ligands, also act as effective antifungal agents against several Aspergillus and Can dida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 1.8-5 mug/mL. The mechan ism of antifungal action of these complexes seem to be unconnected with inh ibition of lanosterol-14-alpha -demethylase, since the levels of sterols as sessed in the fungi cultures were equal in the absence or in the presence o f the tested compounds. Probably the new complexes act as inhibitors of pho sphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls .