Sulphonamide inhibition studies of the β-carbonic anhydrase GsaCAβ present in the salmon platyhelminth parasite Gyrodactylus salaris

Abstract

A β-class carbonic anhydrase (CA, EC 4.2.1.1) present in the genome of the Monogenean platyhelminth Gyrodactylus salaris, a fish parasite, GsaCAβ, has been investigated for its inhibitory effects with a panel of sulphonamides and sulfamates, some of which in clinical use. Several effective GsaCAβ inhibitors were identified, belonging to simple heterocyclic sulphonamides, the deacetylated precursors of acetazolamide and methazolamide (K_Isof 81.9–139.7 nM). Many other simple benezene sulphonamides and clinically used agents, such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, benzolamide, sulthiame and hydrochlorothiazide showed inhibition constants <1 µM. The least effective GsaCAβ inhibitors were 4,6-disubstituted-1,3-benzene disulfonamides, with K_Is in the range of 16.9–24.8 µM. Although no potent GsaCAβ-selective inhibitors were detected so far, this preliminary investigation may be helpful for better understanding the inhibition profile of this parasite enzyme and for the potential development of more effective and eventually parasite-selective inhibitors.

Keywords:

• Carbonic anhydrase
• Gyrodactylus salaris
• kinetics
• sulphonamide inhibitors
• sulfamate

Disclosure statement

CT Supuran is Editor-in-Chief of the Journal of Enzyme Inhibition and Medicinal Chemistry. He was not involved in the assessment, peer review, or decision-making process of this paper. The authors have no relevant affiliations of financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This research was financed by the Italian Ministry for Education and Science (MIUR), grant PRIN: rot. 2017XYBP2R; Ente Cassa di Risparmio di Firenze (ECRF), grant CRF2020.1395 (to CTS); Academy of Finland (to SP); Jane & Aatos Erkko Foundation (to SP); Finnish Cultural Foundation (AA), and Tampere Tuberculosis Foundation (AA).