Journal
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume 35, Issue 1, Pages 65-71Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2019.1683007
Keywords
?-carbonic anhydrase; monothiocarbamates (MTCs); dithiocarbamate (DTCs); in?vitro inhibition; zebrafish larvae
Funding
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- Finnish Cultural Foundation
- Academy of Finland
- Jane and Aatos Erkko Foundation
- Orion-Farmos Foundation
- Tampere Tuberculosis Foundation
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We investigated a panel of 14 compounds belonging to the monothiocarbamate (MTC) and dithiocarbamate (DTC) series against the ?-carbonic anhydrase 3 (?-CA3) of Mycobacterium tuberculosis (Mtb). We also evaluated all compounds for toxicity using 1?5-day post fertilisation zebrafish embryos. 11 out of the 14 investigated derivatives showed effective nanomolar or submicromolar in?vitro inhibition against the ?-CA3 (K(I)s 2.4?812.0?nM), and among them four DTCs of the series (8?10 and 12) showed very significant inhibition potencies with K(I)s between 2.4 and 43?nM. Out of 14 compounds screened for toxicity and safety 9 compounds showed no adverse phenotypic effects on the developing zebrafish larvae at five days of exposure. The results of in?vitro inhibition and the toxicological evaluation of our study suggest that 5 compounds are suitable for further in?vivo preclinical characterisation in zebrafish model.
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