Inhibition of Schistosoma Mansoni Carbonic Anhydrase by the Antiparasitic Drug Clorsulon: X-ray Crystallographic and in Vitro Studies

Overview

Journal Acta Crystallogr D Struct Biol

Specialty Biochemistry

Date 2022 Mar 2

PMID 35234146

Authors

Marta Ferraroni

Andrea Angeli

Simone Carradori

Claudiu T Supuran

Affiliations

Soon will be listed here.

Abstract

Clorsulon is an anthelmintic drug that is clinically used against Fasciola hepatica. Due to the presence of two sulfonamide moieties in its core nucleus, which are well recognized as zinc-binding groups, it was proposed that it may be efficacious in the inhibition of parasite carbonic anhydrases (CAs). Proteomic analyses revealed the presence of CA in the tegument of Schistosoma mansoni, and recently the druggability of this target was explored by testing the inhibitory activities of several sulfonamide-based derivatives. According to the principles of drug repurposing, the aim was to demonstrate a putative new mechanism of action of clorsulon and thus widen its antiparasitic spectrum. For this purpose, the inhibitory activity and isoform selectivity of clorsulon was studied using human CA I and S. mansoni CA, revealing different modes of binding of clorsulon that explain its inhibitory potency against the two enzymes. The information obtained in this study could be crucial in the design of more active and selective derivatives.

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