Schistosoma mansoni is an intestinal parasite with one β-class carbonic anhydrase, SmaBCA. We report the sequence enhancing, production, catalytic activity, and inhibition results of the recombinant SmaBCA. It showed significant catalytic activity on CO2 hydration in vitro with k cat 1.38 × 105 s−1 and k cat/Km 2.33 × 107 M−1 s−1. Several sulphonamide inhibitors, from which many are clinically used, showed submicromolar or nanomolar inhibitory effects on SmaBCA. The most efficient inhibitor with a KI of 43.8 nM was 4-(2-amino-pyrimidine-4-yl)-benzenesulfonamide. Other effective inhibitors with KI s in the range of 79.4–95.9 nM were benzolamide, brinzolamide, topiramate, dorzolamide, saccharin, epacadostat, celecoxib, and famotidine. The other tested compounds showed at least micromolar range inhibition against SmaBCA. Our results introduce SmaBCA as a novel target for drug development against schistosomiasis, a highly prevalent parasitic disease.

Cloning, characterization, and inhibition of the novel β-carbonic anhydrase from parasitic blood fluke, Schistosoma mansoni / Haapanen S.; Angeli A.; Tolvanen M.; Emameh R.Z.; Supuran C.T.; Parkkila S.. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - ELETTRONICO. - 38:(2023), pp. 2184299.2184299-2184299.2184299. [10.1080/14756366.2023.2184299]

Cloning, characterization, and inhibition of the novel β-carbonic anhydrase from parasitic blood fluke, Schistosoma mansoni

Angeli A.;Supuran C. T.;
2023

Abstract

Schistosoma mansoni is an intestinal parasite with one β-class carbonic anhydrase, SmaBCA. We report the sequence enhancing, production, catalytic activity, and inhibition results of the recombinant SmaBCA. It showed significant catalytic activity on CO2 hydration in vitro with k cat 1.38 × 105 s−1 and k cat/Km 2.33 × 107 M−1 s−1. Several sulphonamide inhibitors, from which many are clinically used, showed submicromolar or nanomolar inhibitory effects on SmaBCA. The most efficient inhibitor with a KI of 43.8 nM was 4-(2-amino-pyrimidine-4-yl)-benzenesulfonamide. Other effective inhibitors with KI s in the range of 79.4–95.9 nM were benzolamide, brinzolamide, topiramate, dorzolamide, saccharin, epacadostat, celecoxib, and famotidine. The other tested compounds showed at least micromolar range inhibition against SmaBCA. Our results introduce SmaBCA as a novel target for drug development against schistosomiasis, a highly prevalent parasitic disease.
2023
38
2184299
2184299
Haapanen S.; Angeli A.; Tolvanen M.; Emameh R.Z.; Supuran C.T.; Parkkila S.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1305537
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