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Toxicity evaluation of sulfamides and coumarins that efficiently inhibit human carbonic anhydrases.
Journal of Enzyme inhibition and Medicinal Chemistry ( IF 5.6 ) Pub Date : 2020-09-17 , DOI: 10.1080/14756366.2020.1822829
Ashok Aspatwar 1, 2 , Emanuela Berrino 2 , Silvia Bua 2 , Fabrizio Carta 2 , Clemente Capasso 3 , Seppo Parkkila 1, 4, 5 , Claudiu T Supuran 2
Affiliation  

Here, we report a toxicity study, conducted on zebrafish larvae, of a series of coumarin and sulfamide compounds that were previously reported as inhibitors of human (h) metalloenzymes, carbonic anhydrases (CAs, EC 4.2.1.1). Due to the high relevance of hCA inhibitors as theragnostic agents, it is of pivotal importance to address safety issues that may arise from the initial in vivo toxicological assessment using zebrafish, a relevant model for biomedical research. None of the reported compounds showed adverse phenotypic effects or tissue damage on developing zebrafish larvae after 5 days of exposure. Our study suggests that the coumarin and sulfamide derivatives considered here are safe and suitable for further development and testing.



中文翻译:

有效抑制人碳酸酐酶的磺酰胺和香豆素的毒性评估。

在这里,我们报告了对斑马鱼幼虫进行的一系列香豆素和磺酰胺化合物的毒性研究,这些香豆素和磺酰胺化合物先前被报道为人(h)金属酶,碳酸酐酶(CAs,EC 4.2.1.1)的抑制剂。由于hCA抑制剂作为Theragnostic药物具有高度相关性,因此解决可能因使用斑马鱼(一种生物医学研究的相关模型)进行的体内体内毒理学评估而引起的安全性问题至关重要。暴露5天后,没有化合物对发育中的斑马鱼幼虫表现出不良的表型作用或组织损伤。我们的研究表明,此处考虑的香豆素和磺酰胺衍生物是安全的,适合进一步开发和测试。

更新日期:2020-09-20
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