The almost empty armamentarium to treat schistosomiasis, a neglected parasitic disorder caused by trematode flatworms of the genus Schistosoma, except Praziquantel (PZQ), urged to find new alternatives to fight this infection. Carbonic Anhydrase from Schistosoma mansoni (SmCA) is a possible new target against this nematode. Here, we propose new PZQ derivatives bearing a primary sulphonamide group in order to obtain hybrid drugs. All compounds were evaluated for their inhibition profiles on both humans and Schistosoma CAs, X-ray crystal data of SmCA and hCA II in adduct with some inhibitors were obtained allowing the understanding of the main structural factors responsible of activity. The compounds showed in vitro inhibition of immature and adult S. mansoni, but further optimisation is required for improved activity.

Development of Praziquantel sulphonamide derivatives as antischistosomal drugs / Angeli A.; Ferraroni M.; Carta F.; Haberli C.; Keiser J.; Costantino G.; Supuran C.T.. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - ELETTRONICO. - 37:(2022), pp. 1479-1494. [10.1080/14756366.2022.2078970]

Development of Praziquantel sulphonamide derivatives as antischistosomal drugs

Angeli A.;Ferraroni M.;Carta F.;Supuran C. T.
2022

Abstract

The almost empty armamentarium to treat schistosomiasis, a neglected parasitic disorder caused by trematode flatworms of the genus Schistosoma, except Praziquantel (PZQ), urged to find new alternatives to fight this infection. Carbonic Anhydrase from Schistosoma mansoni (SmCA) is a possible new target against this nematode. Here, we propose new PZQ derivatives bearing a primary sulphonamide group in order to obtain hybrid drugs. All compounds were evaluated for their inhibition profiles on both humans and Schistosoma CAs, X-ray crystal data of SmCA and hCA II in adduct with some inhibitors were obtained allowing the understanding of the main structural factors responsible of activity. The compounds showed in vitro inhibition of immature and adult S. mansoni, but further optimisation is required for improved activity.
37
1479
1494
Angeli A.; Ferraroni M.; Carta F.; Haberli C.; Keiser J.; Costantino G.; Supuran C.T.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1288734
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