Structural Insights into Schistosoma mansoni Carbonic Anhydrase (SmCA) Inhibition by Selenoureido-Substituted Benzenesulfonamides

Tegumental
carbonic anhydrase from the worm Schistosoma
mansoni (SmCA) is considered a new anti-parasitic
target because suppressing its expression interferes with schistosome
metabolism and virulence. Here, we present the inhibition profiles
of selenoureido compounds on recombinant SmCA and resolution of the
first X-ray crystal structures of SmCA in adduct with a selection
of such inhibitors. The key molecular features of such compounds in
adduct with SmCA were obtained and compared to the human isoform hCA
II, in order to understand the main structural factors responsible
for enzymatic affinity and selectivity. Compounds that more specifically
inhibited the schistosome versus human enzymes were identified. The
results expand current knowledge in the field and pave the way for
the development of more potent antiparasitic agents in the near future.