Síntese e avaliação da atividade esquistossomicida de derivados simétricos e assimétricos da dibenzalacetona

Abstract

Schistosomiasis is a Neglected Tropical Disease caused by parasites of the genus Schistosoma, with freshwater mollusks serving as intermediate hosts and humans as definitive hosts. It is estimated that approximately 200,000 people die annually due to infections caused by this parasite. In Brazil, schistosomiasis mansoni is the most prevalent form affecting about 1.5 million brazilians live in at-risk areas, mainly in the northeastern and southeastern. Currently, the World Health Organization (WHO) recommends only praziquantel as the treatment, however, it presents limitations, side effects and the risk of resistance development. Studies using turmeric extract have revealed significant antischistosomal potential. Nevertheless, the antischistosomal activity of dibenzalacetone (DBA), an α,β-unsaturated monocarbonyl derivative of curcumin (the main polyphenol found in tumeric) had not been explored until now, despite its demonstrated antiparasitic activity against other diseases. Thus, this study was synthesized, characterized and evaluated the in vitro anti-Schistosoma mansoni potential of 44 symmetric and asymmetric DBAs. Initially, curcumin and DBAs 16-39, 42-48, 51-54, 56 and 60-62 were incubated in vitro with adult S. mansoni in a preliminary test. The results demonstrated that 8 DBAs showed promising activity, being capable of causing 100% mortality of adult schistosomes after 72 hours of incubation at a concentration of 50 μM. Among them, DBA 16 stood out, which, after 72 hours of incubation, eliminated all adult parasites and significantly reduced their motor activity at a concentration of 6.25 μM. From these results, schistosomicidal activity was determined for curcumin and DBAs 16, 20, 24, 26, 36, 37, 53 and 61 and the results were expressed in EC50 which ranged from 2.1 to 28.4 M. In this study, DBA 16 was the most potent substance, presenting an EC50 of 2.1 ± 0.3 M and IS greater than 95, being, to date, the compound with the most significant schistosomicidal action and greater selectivity for S. mansoni. From the results, an analysis of the relationship between the chemical structure of DBAs and schistosomicidal activity indicated that propanone derivatives and the presence of electron-donating groups at positions 2 and 4 of the aromatic ring play a significant role in schistosomicidal activity.