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 potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), being at the same time structurally similar to the antimicrobial sulfonamides. Here we report that the reaction of aminobenzolamide with arylsulfonyl isocyanates affords a series of new arylsulfonylureido derivatives which were subsequently used as ligands (in the form of conjugate bases, as sulfonamide 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 (isozymes I, II and IV). The newly synthesized complexes, unlike the free ligands, also 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 1.8-5 microg/mL. The mechanism of antifungal action of these complexes seem to be unconnected with inhibition of lanosterol-14-alpha-demethylase, since the levels of sterols assessed in the fungi cultures were equal in the absence or in the presence of the tested compounds. Probably the new complexes act as inhibitors of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls.
Mastrolorenzo
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Università degli Studi, Dipartimento di Scienze Dermatologiche, Centro MTS, Firenze, Italia.
Scozzafava
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Supuran
C T
CT
D062365:Aminobenzoates / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D001574:Benzolamide / Q000138:chemical synthesis / Q000494:pharmacology; D002175:Candida / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008359:Mannose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors; D008826:Microbial Sensitivity Tests; D012834:Silver / Q000737:chemistry; D013261:Sterols / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry
D062365:Aminobenzoates; D000935:Antifungal Agents; D002257:Carbonic Anhydrase Inhibitors; D008024:Ligands; D013261:Sterols; D013449:Sulfonamides; D013830:Thiadiazoles; D012834:Silver; D002256:Carbonic Anhydrases; D008359:Mannose-6-Phosphate Isomerase; D001574:Benzolamide; D015032:Zinc