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

作者：Guglielmo Stefano; Cortese Daniela; Vottero Francesca; Rolando Barbara; Kommer Valerie P; Williams David L^*; Fruttero Roberta; Gasco Alberto

来源：European Journal of Medicinal Chemistry, 2014, 84: 135-145.

DOI：10.1016/j.ejmech.2014.07.007

• Furoxans
• Praziquantel
• Schistosomiasis
• Thioredoxin glutathione reductase
• NO-donor praziquantel

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.

• 出版日期2014-9-12