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

Abstract

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.