Schistosomicidal evaluation of synthesized bromo and nitro chalcone derivatives

Abstract

Chalcones are compounds associated to several biological activities. The modification of chemical structures is one of the most widely used tool in the pharmaceutical industry to obtain new drugs. In this study, we synthetized chalcones with nitro and bromo substituents in different positions in the aromatic rings. NMR spectroscopy was used for characterization. Simultaneously, a conformational study of the compounds was carried out employing theoretical calculations. Furthermore, the schistosomicidal in vitro effect of bromo and nitro chalcone substituents on adult Schistosoma mansoni was investigated. The results showed that most chalcones have a conformational preference for s-cis geometry, which is favored by the conjugative effect of electronic delocalization. However, chalcones with ortho substituents dissipate greater stabilization of s-trans conformations, possibly for favoring surfaces with weak interactions such as Van der Waals. In addition, a significant effect of chalcones on female and male S. mansoni was observed. All samples evaluated reduced the motor activity of worms, caused mortality in male and female worms, and resulted in morphological alterations in a concentration- dependent manner (25–200 μg/mL) in a period of 6–24 h of incubation. Additionally, chalcones influenced the separation of couple worms and suppressed egg production at sublethal concentrations. Our results demonstrated that chalcones present potential to be used as schistosomicidal drugs, contributing to the clarification of the relation between the molecule conformation and the associated biological effects.