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. 2017 Dec;32(1):1064-1070.
doi: 10.1080/14756366.2017.1355307.

Inhibition of the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa with monothiocarbamates

Alessio Nocentini  1   2 , Daniela Vullo  3 , Sonia Del Prete  1   4 , Sameh M Osman  5 , Fatmah A S Alasmary  5 , Zeid AlOthman  5 , Clemente Capasso  4 , Fabrizio Carta  1 , Paola Gratteri  2 , Claudiu T Supuran  1
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Inhibition of the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa with monothiocarbamates

Alessio Nocentini et al. J Enzyme Inhib Med Chem. 2017 Dec.

Abstract

A series of monothiocarbamates (MTCs) was investigated for the inhibition of the β-class carbonic anhydrase (CAs, EC 4.2.1.1) from the fungal parasite Malassezia globosa, MgCA. These MTCs incorporate various scaffolds, among which aliphatic amine with 1-4 carbons atom in their molecule, morpholine, piperazine, as well as phenethylamine and benzylamine derivatives. All the reported MTCs displayed a better efficacy in inhibiting MgCA compared to the clinically used sulphonamide drug acetazolamide (KI of 74 μM), with KIs spanning between 1.85 and 18.9 μM. The homology model of the enzyme previously reported by us was used to rationalize the results by docking some of these MTCs within the fungal CA active site. This study might be useful to enrich the knowledge of the MgCA inhibition profile, eliciting novel ideas pertaining the design of modulators with potential efficacy in combatting dandruff or other fungal infections.

Keywords: Carbonic anhydrase; Malassezia globosa; inhibitor; monothiocarbamate; β-CA-class enzyme.

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Figures

Figure 1.
Figure 1.
(a) ESP atomic charges of 2 derived from a B3LYP/6–31 G*+. Red colour represents negative values of the electrostatic potential (b) Schematic representation of the binding mode of MTCs into the MgCA active site.
Figure 2.
Figure 2.
Docked orientations of compounds 2 and 9 (a); 8 (b) and 10 (c) within MgCA active site. Monomer A and B are coloured blue and green, respectively.
See this image and copyright information in PMC

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