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Natural Polyphenols Selectively Inhibit β‐Carbonic Anhydrase from the Dandruff‐Producing Fungus Malassezia globosa : Activity and Modeling Studies
Author(s) -
Nocentini Alessio,
Bua Silvia,
Del Prete Sonia,
Heravi Yeganeh Entezari,
Saboury Ali A.,
Karioti Anastasia,
Bilia Anna Rita,
Capasso Clemente,
Gratteri Paola,
Supuran Claudiu T.
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800015
Subject(s) - biochemistry , chemistry , enzyme , carbonic anhydrase , dandruff , biology , organic chemistry , shampoo
Around 50 % of the worldwide population is affected by dandruff, which is triggered by a variety of factors. The yeast Malassezia globosa has been labeled as the most probable causative agent for the onset of dandruff. The β‐carbonic anhydrase (CA) of MgCA was recently validated as an anti‐dandruff target, with its inhibition being responsible for in vivo growth defects in the fungus. As classical CA inhibitors of the sulfonamide type give rise to permeability problems through biological membranes, finding non‐sulfonamide alternatives for MgCA inhibition is of considerable interest in the cosmetic field. We recently screened a large library of human (h) CA inhibitors for MgCA inhibition, including different chemotypes, such as monothiocarbamates, dithiocarbamates, phenols, and benzoxaboroles. Herein, we expanded the research toward new MgCA inhibitors by considering a set of natural polyphenols (including flavones, flavonols, flavanones, flavanols, isoflavones, and depsides) that exhibited MgCA inhibitory activity in the micromolar range, as well as selectivity for the fungal isozyme over off‐target human isoforms. The binding mode of representative derivatives within the MgCA catalytic cleft was investigated by docking studies using a homology‐built model.