title: Carbonic anhydrase inhibitors. Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with branched aliphatic/aromatic carboxylates and their derivatives.
abstract: The inhibition of the β-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with a series of 25 branched aliphatic and aromatic carboxylates has been investigated. Human isoforms hCA I and II were also included in the study for comparison. Aliphatic carboxylates were generally millimolar hCA I and II inhibitors and low micromolar/submicromolar β-CA inhibitors. Aromatic carboxylates were micromolar inhibitors of the four enzymes but some of them showed low nanomolar activity against the fungal pathogenic enzymes. 4-Hydroxy- and 4-methoxy-benzoate inhibited Can2 with K(I)s of 9.5-9.9 nM. The methyl esters, hydroxamates, hydrazides and carboxamides of some of these derivatives were also effective inhibitors of the α- and β-CAs investigated here.
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.forename: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Hall
authors.forename: Fritz A
authors.initials: FA
authors.lastname: Mühlschlegel
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002176:Candida albicans / Q000201:enzymology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003455:Cryptococcus neoformans / Q000201:enzymology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002264:Carboxylic Acids; D005656:Fungal Proteins; D002256:Carbonic Anhydrases