title: Dithiocarbamates effectively inhibit the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa.
abstract: A series of dithiocarbamates (DTCs) was investigated for the inhibition of the β-class carbonic anhydrase (CAs, EC 4.2.1.1) from the fungal parasite Malassezia globosa, MgCA, a validated anti-dandruff drug target. These DTCs incorporate various scaffold, among which those of N,N-dimethylaminoethylenediamine, the aminoalcohols with 3-5 carbon atoms in their molecule, 3-amino-quinuclidine, piperidine, morpholine and piperazine derivatives, as well as phenethylamine and its 4-sulfamoylated derivative. Several DTCs resulted more effective in inhibiting MgCA compared to the standard sulfonamide drug acetazolamide (KIof 74μM), with KIs ranging between 383 and 6235nM. A computational approach, involving a homology modeling of the enzyme and docking inhibitors within its active site, helped us rationalize the results. This study may contribute to better understand the inhibition profile of MgCA, and offer new ideas for the design of modulators of activity which belong to less investigated chemical classes, thus potentially useful to combat dandruff and other fungal infections.
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Sesto Fiorentino, Firenze, Italy; Istituto di Bioscienze e Biorisorse (IBBR)-CNR, Via P. Castellino 111, 80131 Napoli, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Del Prete
authors.affiliation: Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Sesto Fiorentino, Firenze, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Nocentini
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Sameh M
authors.initials: SM
authors.lastname: Osman
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Zeid
authors.initials: Z
authors.lastname: AlOthman
authors.affiliation: Istituto di Bioscienze e Biorisorse (IBBR)-CNR, Via P. Castellino 111, 80131 Napoli, Italy.
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Murat
authors.initials: M
authors.lastname: Bozdag
authors.affiliation: Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Sesto Fiorentino, Firenze, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.affiliation: Università degli Studi di Firenze, Department Neurofarba - Pharmaceutical and Nutraceutical Section, Laboratory of Molecular Modeling Cheminformatics & QSAR, via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Gratteri
authors.affiliation: Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Sesto Fiorentino, Firenze, Italy; Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008290:Malassezia / Q000201:enzymology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013859:Thiocarbamates; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; Dithiocarbamate; Inhibitor; Malassezia globosa; β-CA-class enzyme