Toxicity evaluation of sulfamides and coumarins that efficiently inhibit human carbonic anhydrases

Abstract

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.

Keywords:

• Carbonic anhydrases
• inhibitors
• toxicity screening
• zebrafish

Acknowledgements

We thank Aulikki Lehmus and Marianne Kuuslahti for the histochemical analyses of the zebrafish samples. We also thank the Tampere Zebrafish Core Facility, partly funded by Biocenter Finland, for maintaining and providing the zebrafish. FC is grateful to “Bando di Ateneo per il Finanziamento di Progetti Competitivi per Ricercatori a Tempo Determinato (RTD) dell’Università di Firenze - 2020-2021,” which partially funded this work.

Disclosure statement

The authors declare no competing interests.

Additional information

Funding

This work was partly funded by Biocenter Finland. This work was also supported by grants from the Finnish Cultural Foundation and Tampere Tuberculosis Foundation (AA), Academy of Finland (SP), and Jane & Aatos Erkko Foundation (SP).