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



: Haapanen Susanna, Angeli Andrea, Tolvanen Martti, Emameh Reza Zolfaghari, Supuran Claudiu T, Parkkila Seppo

Publisher: TAYLOR & FRANCIS LTD

: 2023

: Journal of Enzyme Inhibition and Medicinal Chemistry

: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

: J ENZYM INHIB MED CH

:  2184299

: 38

: 1

: 12

: 1475-6366

DOI: https://doi.org/10.1080/14756366.2023.2184299

: https://www.tandfonline.com/doi/full/10.1080/14756366.2023.2184299

: https://research.utu.fi/converis/portal/detail/Publication/178960544


Schistosoma mansoni is an intestinal parasite with one beta-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 x 10(5) s(-1) and k (cat)/K-m 2.33 x 10(7) 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 K-I of 43.8 nM was 4-(2-amino-pyrimidine-4-yl)-benzenesulfonamide. Other effective inhibitors with K-I 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.

Last updated on 2024-26-11 at 20:44