We investigated a panel of 14 compounds belonging to the monothiocarbamate (MTC) and dithiocarbamate (DTC) series against the β-carbonic anhydrase 3 (β-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 β-CA3 (KIs 2.4-812.0 nM), and among them four DTCs of the series (8-10 and 12) showed very significant inhibition potencies with KIs 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.

中文翻译：

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单硫代和二硫代氨基甲酸酯对结核分枝杆菌β-碳酸酐酶3的体外抑制作用，并使用斑马鱼发育中的胚胎评估其毒性。

我们调查了针对结核分枝杆菌（Mtb）的β-碳酸酐酶3（β-CA3）的14种化合物，分别属于一硫代氨基甲酸酯（MTC）和二硫代氨基甲酸酯（DTC）系列。我们还使用了受精后的1-5天斑马鱼胚胎评估了所有化合物的毒性。在研究的14种衍生物中，有11种表现出对β-CA3的有效纳摩尔或亚微摩尔体外抑制作用（KIs 2.4-812.0 nM），其中四个DTC系列（8-10和12）对KIs表现出非常显着的抑制作用在2.4至43 nM之间。在14种化合物的毒性和安全性筛选中，有9种化合物在暴露5天后对发育中的斑马鱼幼虫没有不利的表型作用。