A beta-class carbonic anhydrase (CA, EC 4.2.1.1) present in the genome of the Monogenean platyhelminth Gyrodactylus salaris, a fish parasite, GsaCA beta, has been investigated for its inhibitory effects with a panel of sulphonamides and sulfamates, some of which in clinical use. Several effective GsaCA beta inhibitors were identified, belonging to simple heterocyclic sulphonamides, the deacetylated precursors of acetazolamide and methazolamide (K (I)sof 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 mu M. The least effective GsaCA beta inhibitors were 4,6-disubstituted-1,3-benzene disulfonamides, with K (I)s in the range of 16.9-24.8 mu M. Although no potent GsaCA beta-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.

Sulphonamide inhibition studies of the β-carbonic anhydrase GsaCAβ present in the salmon platyhelminth parasite Gyrodactylus salaris / Aspatwar, Ashok; Bonardi, Alessandro; Aisala, Heidi; Zueva, Ksenia; Primmer, Craig R; Lumme, Jaakko; Parkkila, Seppo; Supuran, Claudiu T. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - ELETTRONICO. - 38:(2023), pp. 0-0. [10.1080/14756366.2023.2167988]

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

Bonardi, Alessandro;Supuran, Claudiu T
2023

Abstract

A beta-class carbonic anhydrase (CA, EC 4.2.1.1) present in the genome of the Monogenean platyhelminth Gyrodactylus salaris, a fish parasite, GsaCA beta, has been investigated for its inhibitory effects with a panel of sulphonamides and sulfamates, some of which in clinical use. Several effective GsaCA beta inhibitors were identified, belonging to simple heterocyclic sulphonamides, the deacetylated precursors of acetazolamide and methazolamide (K (I)sof 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 mu M. The least effective GsaCA beta inhibitors were 4,6-disubstituted-1,3-benzene disulfonamides, with K (I)s in the range of 16.9-24.8 mu M. Although no potent GsaCA beta-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.
2023
38
0
0
Aspatwar, Ashok; Bonardi, Alessandro; Aisala, Heidi; Zueva, Ksenia; Primmer, Craig R; Lumme, Jaakko; Parkkila, Seppo; Supuran, Claudiu T
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1305973
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