title: Dithiocarbamates with potent inhibitory activity against the Saccharomyces cerevisiae β-carbonic anhydrase.
abstract: Dithiocarbamates (DTCs) prepared from primary or secondary amines, which incorporated amino/hydroxyl-alkyl, mono-/bicyclic aliphatic/heterocyclic rings based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, were investigated for the inhibition of α- and β-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, such as the human (h) isoform hCA I and II, as well as the Saccharomyces cerevisiae β-CA, scCA. The yeast and its β-CA were shown earlier to be useful models of pathogenic fungal infections. The DTCs investigated here were medium potency hCA I inhibitors (K(I)s of 66.5-910 nM), were more effective as hCA II inhibitors (K(I)s of 8.9-107 nM) and some of them showed excellent, low nanomolar activity against the yeast enzyme, with inhibition constants ranging between 6.4 and 259 nM. The detailed structure activity relationship for inhibition of the yeast and human enzymes is discussed. Several of the investigated DTCs showed excellent selectivity ratios for inhibiting the yeast over the human cytosolic CA isoforms.
authors: a Laboratorio di Chimica Bioinorganica, Dipartimento di Chimica , Università degli Studi di Firenze , Sesto Fiorentino , Florence , Italy .
authors: Murat
authors: M
authors: Bozdag
authors: a Laboratorio di Chimica Bioinorganica, Dipartimento di Chimica , Università degli Studi di Firenze , Sesto Fiorentino , Florence , Italy .
authors: Fabrizio
authors: F
authors: Carta
authors: a Laboratorio di Chimica Bioinorganica, Dipartimento di Chimica , Università degli Studi di Firenze , Sesto Fiorentino , Florence , Italy .
authors: Daniela
authors: D
authors: Vullo
authors: a Laboratorio di Chimica Bioinorganica, Dipartimento di Chimica , Università degli Studi di Firenze , Sesto Fiorentino , Florence , Italy .
authors: Semra
authors: S
authors: Isik
authors: b Department of Chemistry, College of Science , King Saud University , Riyadh , Saudi Arabia , and.
authors: Zeid
authors: Z
authors: AlOthman
authors: b Department of Chemistry, College of Science , King Saud University , Riyadh , Saudi Arabia , and.
authors: Sameh M
authors: SM
authors: Osman
authors: a Laboratorio di Chimica Bioinorganica, Dipartimento di Chimica , Università degli Studi di Firenze , Sesto Fiorentino , Florence , Italy .
authors: Andrea
authors: A
authors: Scozzafava
authors: a Laboratorio di Chimica Bioinorganica, Dipartimento di Chimica , Università degli Studi di Firenze , Sesto Fiorentino , Florence , Italy .|c Sezione di Scienze Farmaceutiche, Dipartimento NEUROFARBA , Università degli Studi di Firenze , Sesto Fiorentino , Florence , Italy.
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013859:Thiocarbamates; D002256:Carbonic Anhydrases
keywords: Saccharomyces cerevisiae; carbonic anhydrase; dithiocarbamate; inhibitor; β-Class enzyme