The critical CO2 hydration reaction to bicarbonate and protons is catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1). Their physiological role is to assist the transport of the CO2 and HCO3- at the cellular level, which will not be ensured by the low velocity of the uncatalyzed reaction. CA inhibition may impair the growth of microorganisms. In the yeasts, Candida albicans and Malassezia globosa, the activity of the unique β-CA identified in their genomes was demonstrated to be essential for growth of the pathogen. Here, we decided to investigate the sulfonamide inhibition profile of the homologous β-CA (MreCA) identified in the genome of Malassezia restricta, an opportunistic pathogen triggering dandruff and seborrheic dermatitis. Among 40 investigated derivatives, the best MreCA sulfonamide inhibitors were dorzolamide, brinzolamide, indisulam, valdecoxib, sulthiam, and acetazolamide (KI < 1.0 μM). The MreCA inhibition profile was different from those of the homologous enzyme from Malassezia globosa (MgCA) and the human isoenzymes (hCA I and hCA II). These results might be useful to for designing CA inhibitor scaffolds that may selectively inhibit the dandruff-producing fungi.

中文翻译：

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产自头孢病的机会病原菌马拉色霉菌β-碳酸酐酶的磺酰胺抑制作用。

碳酸酐酶（CAs，EC 4.2.1.1）催化关键的CO2水合反应生成碳酸氢盐和质子。它们的生理作用是在细胞水平上协助CO2和HCO3-的运输，而未催化反应的低速度将无法确保这一点。CA抑制可能会损害微生物的生长。在酵母中，白色念珠菌和球形疟原虫在基因组中鉴定出的独特β-CA活性对病原体的生长至关重要。在这里，我们决定研究在限制马拉丝菌中的同源β-CA（MreCA）的磺酰胺抑制特​​性，马拉丝菌是引发头皮屑和脂溢性皮炎的机会病原体。在研究的40种衍生物中，最好的MreCA磺酰胺抑制剂为多佐胺，布林酰胺，吲哚拉姆，伐地昔布，舒马坦和乙酰唑胺（KI <1.0μM）。MreCA抑制谱不同于球形马拉色菌（MgCA）和人同工酶（hCA I和hCA II）的同源酶。这些结果对于设计可选择性抑制产生头皮屑的真菌的CA抑制剂支架可能有用。