期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 22, 期 2, 页码 859-862出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.12.033
关键词
Carbonic anhydrase; Dithiocarbamate; Beta-class enzyme; Inhibitor; Cryptococcus neoformans; Candida albicans; Candida glabrata
资金
- EU
- MRC [G0601049] Funding Source: UKRI
- Medical Research Council [G0601049] Funding Source: researchfish
A series of N-mono- and N,N-disubstituted dithiocarbamates have been investigated as inhibitors of three beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the fungal pathogens Cryptococcus neoformans, Candida albicans and Candida glabrata, that is, Can2. CaNce103 and CgNce103, respectively. These enzymes were inhibited with efficacies between the subnanomolar to the micromolar range, depending on the substitution pattern at the nitrogen atom from the dithiocarbamate zinc-binding group. This new class of beta-CA inhibitors may have the potential for developing antifungal agents with a diverse mechanism of action compared to the clinically used drugs for which drug resistance was reported, and may also explain the efficacy of dithiocarbamates as agricultural antifungal agents. (C) 2011 Elsevier Ltd. All rights reserved.
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