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Cloning, Characterization, and Inhibition of the Novel β-Carbonic Anhydrase from Parasitic Blood Fluke, Schistosoma mansoni
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  • Susanna Haapanen,
  • Andrea Angeli,
  • Martti Tolvanen,
  • Reza Zolfaghari Emameh,
  • Claudiu T. Supuran,
  • Seppo Parkkila
Susanna Haapanen
Tampereen yliopisto

Corresponding Author:[email protected]

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Andrea Angeli
Universita degli Studi di Firenze
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Martti Tolvanen
Turun yliopisto
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Reza Zolfaghari Emameh
National Institute for Genetic Engineering and Biotechnology
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Claudiu T. Supuran
Universita degli Studi di Firenze
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Seppo Parkkila
Tampereen yliopisto
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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 CO 2 hydration in vitro with k cat 1.38 x 10 5 s -1 and k cat/K m 2.33 x 10 7 M -1 s -1. Several sulfonamide inhibitors, from which many are clinically used, showed submicromolar or nanomolar inhibitory effects on SmaBCA. The most efficient inhibitor with a K I of 43.8 nM was 4-(2-amino-pyrimidine-4-yl)-benzenesulfonamide. Other effective inhibitors with K Is in the range of 79.4 nM-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.