title: Anion inhibition studies of the dandruff-producing fungus Malassezia globosa β-carbonic anhydrase MgCA.
abstract: The genome of the fungal parasite Malassezia globosa, the causative agent of dandruff, contains a single gene annotated as encoding a carbonic anhydrase (CAs, EC 4.2.1.1) belonging to the β-class (MgCA). In an earlier work (J. Med. Chem. 2012, 55, 3513) we have validated this enzyme as an anti-dandruff drug target, reporting that sulfonamide inhibitors show in vitro and in vivo effects, in an animal model of Malassezia infection. However, few classes of compounds apart the sulfonamides, were investigated for their activity against MgCA. Here we present an anion inhibition study of this enzyme, reporting that metal complexing anions such as cyanate, thiocyanate, cyanide, azide are weak MgCA inhibitors (KIs ranging between 6.81 and 45.2 mM) whereas bicarbonate (KI of 0.59 mM) and diethyldithiocarbamate (KI of 0.30 mM) together with sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid were the most effective inhibitors detected so far, with KIs ranging between 83 and 94 μM. This study may help a better understanding of the inhibition profile of this enzyme and may offer the possibility to design new such modulators of activity belonging to different chemical classes.
authors.affiliation: Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Sesto Fiorentino, Firenze, Italy; Istituto di Biochimica delle Proteine-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, 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: Department of Chemistry, College of Science, King Saud University, PO 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, PO Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Zeid
authors.initials: Z
authors.lastname: AlOthman
authors.affiliation: Istituto di Biochimica delle Proteine-CNR, Via P. Castellino 111, 80131 Napoli, Italy. Electronic address: clemente.capasso@ibbr.cnr.it.
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
authors.affiliation: Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Sesto Fiorentino, Firenze, Italy; Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D001639:Bicarbonates / Q000737:chemistry; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000235:genetics; D063807:Dandruff / Q000188:drug therapy; D004050:Ditiocarb / Q000737:chemistry; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008290:Malassezia; D010802:Phylogeny; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D005656:Fungal Proteins; D007527:Isoenzymes; D011994:Recombinant Proteins; D004050:Ditiocarb; D002256:Carbonic Anhydrases
keywords: Anion; Carbonic anhydrase; Inhibitor; Malassezia globosa; β-CA-class enzyme