Planejamento molecular, síntese e atividade esquistossomicida de chalconas e auronas inibidoras da enzima SmATPDase1 de Schistosoma mansoni

Abstract

Schistosomiasis is one of the most prevalent parasitic diseases that occur in many tropical and subtropical countries. Currently, the treatment of schistosomiasis is dependent on a single available drug, praziquantel (PZQ). Thus, new drug choices are needed. In this regard, natural products, especially chalcone and aurone, have exhibited significant in vitro schistosomicidal activities. Therefore, this paper describes the in silico molecular design, synthesis and in vitro schistosomicidal activities of chalcones and aurones analogues. Also, the in vitro Schistosoma mansoni ATPDase1 (SmATPDase1) enzyme inhibitory activity of compounds was investigated. Molecular design was done by docking techniques. In vitro schistosomicidal assays were performed against S. mansoni adult worms, cell viability was measured by MTT assay, and the SmATPDase1 inhibitory activity was determined spectrophotometrically. A total of eight chalcone and three aurone analogues were successfully designed and synthesized. Compounds VR1, VR2, VR8 and VR13 were active at a concentration of 50 uM against adult schistosomes. All active compounds proved to be citotoxic at 100 uM to mamalian cells. Different inhibition profiles were found for the compounds in preliminary assays with SmATPDase1. These results reinforce the potential of chalcones and aurones as schistosomicidal substances. Further studies are needed to correlate the antischistosomal activities presented by the compounds with the enzyme inhibition.