Synthesis and evaluation of catecholic chalcones as potential agents against Schistosoma mansoni

Resumo

Schistosomiasis, a neglected tropical parasitosis, is caused by trematode helminths of the genus Schistosoma. In Brazil, the most affected country by schistosomiasis on the continent, the only species present is Schistosoma mansoni. Praziquantel (PZQ) is the drug of choice, and the only one available, for the treatment of parasitosis. However, long-term and repeated use of PZQ can induce drug resistance or reduce its susceptibility. In this context,  the imminence of PZQ-resistant strains represent a serious public health problem. Thus, there is a need to find new compounds that can be developed into antiparasitic drugs. In this scenario, natural products are presented as a valuable alternative for the investigation of new compounds that have activity against S. mansoni. Chalcones, specialized plant metabolites, are characterized by two phenyl units (A and B rings) linked by a α,β-unsaturated ketone bridge. They are privileged structures by medicinal chemistry because they have concise and versatile syntheses, and a wide spectrum of bioactivities. Within this spectrum, hydroxylated chalcones showed antiparasitic activities against species of Leishmania, Trypanosoma and Plasmodium, as well as schistosomicidal activity. In this work, through aldolic condensation in an acid medium, we synthesized and characterized a series of 18 catecholic chalcones with modifications on A ring. We evaluated the in vitro activity of these compounds at 5 μg/mL, in a period of 72 h. The mortality and viability of the worms were evaluated, the latter parameter was analyzed on a scale of 0 to 3, where 3 do not present changes compared to the control and 0 are dead. Catecholic chalcones 6 and 7 caused 100% mortality of male worms in 72 h, and 100% of female mortality in 48 h and 24 h, respectively. Worms exposed to chalcone 6 displayed a reduced viability (lt;2) in 24 h. Catecholic chalcone 5 demonstrated 100% mortality of males and females in 48 h, and reduced viability of male worms in 6 h of exposure, while in females the reduced viability was observed after 24 h. These results evidenced the potential of catecholic chalcones against S. mansoni and consequently may contribute to the development of new therapeutic agents against schistosomiasis.