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Designing and synthesis of bioactive compounds from marine algae against schistosomiasis


Schistosomiasis is an endemic parasitic disease caused by Schistosoma worms having freshwater snails as intermediate hosts. The disease affects around 250 million people worldwide, and more than 6.8 million in Brazil. These figures show that the elimination of schistosomiasis is far from being achieved. In addition, the chemical arsenal available for treating the disease is limited to two drugs. Praziquantel is the only drug recommended for the treatment and used in the control programs. Although it is safe, praziquantel is not active against young worms and does not prevent reinfection. Resistance has not been reported yet, but the occurrence of less susceptible parasites in laboratory has been observed. In order to control the host molluscs, there is only one molluscicide, named niclosamide, which is effective against adult molluscs and eggs, but it is highly toxic to non target species. Natural products have been indeed considered as an alternative source to find novel active compounds, despite of the lack of interest of the pharmaceutical industries in developing drugs for treating neglected diseases. In our bioprospection studies, we found some interesting Brazilian marine algae species from Laurencia and Dictyota genera showing schistosomicidal and molluscicidal activities. From L. aldingensis, four dihydroceramides were initially selected to perform studies of identification of novel prototypes; active fractions were identified in crude extracts from Dictyota species. The compounds pointed out in the structure-property-biological activity relationship studies will be previously investigated applying molecular modelling and computational chemistry methods in order to drive the experimental procedures to the most promising chemical entities. The most promising compounds will be synthesized using routes that prioritize the principles of Green Chemistry. (AU)