Cloning, Characterization, and Inhibition of the Novel β-Carbonic Anhydrase from Parasitic Blood Fluke, Schistosoma mansoni

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 hydration in vitro with k 1.38 x 10 s and k /K 2.33 x 10 M s . Several sulfonamide inhibitors, from which many are clinically used, showed submicromolar or nanomolar inhibitory effects on SmaBCA. The most efficient inhibitor with a K of 43.8 nM was 4-(2-amino-pyrimidine-4-yl)-benzenesulfonamide. Other effective inhibitors with K s 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.

Perspectives on the Drug Discovery of Intestinal Protozoan Parasites

“…These intestinal infections can be managed by both preventive measures as well as by appropriate drug treatment. For treating different protozoan parasites, only 25 drugs are used in clinical settings [8]. However, even after the latest advancements in the field, such as the availability of the complete genomes and a comprehensive understanding of the life cycles of these pathogens, there are limited translational breakthroughs from the lab to the clinic, and no major new classes of antiprotozoal drugs have been developed.…”