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 (KI of 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.

Dithiocarbamates effectively inhibit the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa / Vullo, Daniela; Del Prete, Sonia; Nocentini, Alessio; Osman, Sameh M.; Alothman, Zeid; Capasso, Clemente; Bozdag, Murat; Carta, Fabrizio; Gratteri, Paola; Supuran, Claudiu T.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 25:(2017), pp. 1260-1265. [10.1016/j.bmc.2016.12.040]

Dithiocarbamates effectively inhibit the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa

VULLO, DANIELA;DEL PRETE, SONIA;NOCENTINI, ALESSIO;BOZDAG, MURAT;CARTA, FABRIZIO;GRATTERI, PAOLA;SUPURAN, CLAUDIU TRANDAFIR
2017

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 (KI of 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.
2017
25
1260
1265
Vullo, Daniela; Del Prete, Sonia; Nocentini, Alessio; Osman, Sameh M.; Alothman, Zeid; Capasso, Clemente; Bozdag, Murat; Carta, Fabrizio; Gratteri, Pa...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1075013
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