Schistosomiasis, one of the most prevalent neglected parasitic diseases affecting humans and animals, is caused by the Platyhelminthes of the genus Schistosoma. Schistosomes are the only trematodes to have evolved sexual dimorphism and the constant pairing with a male is essential for the sexual maturation of the female. Pairing is required for the full development of the two major female organs, ovary and vitellarium that are involved in the production of different cell types such as oocytes and vitellocytes, which represent the core elements of the whole egg machinery. Sexually mature females can produce a large number of eggs each day. Due to the importance of egg production for both life cycle and pathogenesis, there is significant interest in the search for new strategies and compounds not only affecting parasite viability but also egg production. In the search for new compounds active against Schistosoma mansoni, the use of quinone scaffold of marine secondary metabolites [1,2] has represented a chemical starting point to obtain new thiazinoquinone compounds 1-16 (Figure 1). Some of these compounds have already been reported for an interesting antimalarial activity . The synthesis of compounds 1-16 has been achieved in few steps with the reaction between hypotaurine and suitable benzoquinones to give the thiazinoquinone scaffolds as key step [2,3]. We have used a recently developed organism-based approach, based on ATP quantitation in the schistosomula larval stage of S. mansoni  for the screening of the compounds 1-16. In particular 9/16 of the synthetic derivatives demonstrated to be effective at 10 M against schistosomula and, interestingly, they share the same regiochemistry of dioxothiazine ring. In order to identify multistage compounds, the identified active thiazinoquinones in the screening were also assayed on adult worm pairs and 8/9 of these synthetic compounds resulted to be very active. Characterization of the effects of the selected compounds on the morphology of the reproductive organs and on egg development and production is in progress. In conclusion these preliminary results identify the thiazinoquinone chemical scaffold as an excellent starting point for the discovery of novel schistosomicidal compounds.  Aiello, A.; Fattorusso, E.; Luciano, P.; Mangoni, A.; Menna, M. Eur. J. Org. Chem 2005, 23, 5024-5030.  Aiello, A; Fattorusso, E.; Luciano, P.; Menna, M.; Calzado, M. A.; Munoz, E.; Bonadies, F.; Guiso, M.; Sanasi, M. F.; Cocco, G.; Nicoletti, R. Bioorg. Med. Chem. 2010, 18, 719-727.  Imperatore, C.; Persico, M.; Aiello, A.; Luciano, P.; Guiso, M.; Sanasi, M. F.; Taramelli, D.; Parapini, S.; Cebrián-Torrejón, G.; Doménech-Carbó, A.; Fattorusso, C.; Menna, M. RSC Adv. 2015, 5 ,70689-70702.  Lalli, C.; Guidi, A.; Gennari, N.; Altamura, S.; Bresciani, A.; Ruberti, G. PLoS Negl Trop Dis. 2015 J9(1): e0003484. doi: 10.1371/journal.pntd.0003484. eCollection 2015 Jan.
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