New praziquantel derivatives containing NO-donor furoxans and related furazans as active agents against Schistosoma mansoni

•New NO-donor derivatives of praziquantel (PZQ) have been synthesized and studied.•The compounds are potential therapeutic tools against schistosomiasis.•Several compounds showed interesting TGR inhibiting and antiparasitic activities.•The compounds could be useful in case of infection by PZQ-resistant schistosomes.

A series of NO-donor praziquantel hybrid compounds was obtained by combining praziquantel (PZQ) and furoxan moieties in a single entity. NO-donor properties of the furoxan derivatives were evaluated by detecting nitrite after incubation of the products in 7.4 pH buffered solution in the presence of l-cysteine. Structurally-related furazans, devoid of NO release capacity, were also synthesized for control purposes. All products were studied for their ability to inhibit recombinant Schistosoma mansoni thioredoxin glutathione reductase (TGR). Mobility and death of adult Schistosoma mansoni worms cultured in the presence of the products were evaluated versus PZQ. Analysis of the results showed that some products were endowed with both PZQ and NO-dependent antiparasitic properties. Compounds 6, 7, 18, and 24 emerged as the most interesting balanced hybrids, worthy of additional study on PZQ-resistant parasites.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide