Study of EF-24 curcumin analogue and praziquantel in biochemical and morphological aspects involved in the cell death of the Schistosoma mansoni parasite

Abstract

Schistosoma mansoni is a parasite which leads to a condition known as schistosomiasis due to granulomatous reactions formed around the parasite eggs which migrate to the host tissue. The only drug used for the treatment against the parasite is praziquantel, due to its effectiveness, but there are already reports of parasite resistance against the action of the drug. About its mechanism of action in S. mansoni little is known, it is interesting to understand this mechanism, to the search for new substances that may have a similar effect. Curcumin is a phenolic substance extracted from the plant Cúrcuma longa, which has schistosomicidal activity in vitro and in vivo against S. mansoni, and results of our research group showed that in adult worms of S. mansoni, curcumin cause DNA fragmentation, increased activity caspase-3 and increased apoptotic cells when subjected to the TUNEL assay. Studies have shown that by through chemical modifications can be synthesized derivatives and analogs which may have higher activity with respect to some of the substance factors. Our research group has also studied the in vitro effect of EF-24, which is an analog of curcumin, against S. mansoni it was possible to verify that the analogue showed activity schistosomicidal vitro, and cause visible and significant changes in the cells of parasite. This project aims to study which cellular changes occur in S. mansoni after exposure to EF-24 and praziquantel. Therefore, we intend to perform ultrastructural analysis, analysis of the DNA fragmentation in gel, and caspase-3 activity at different times of exposure to EF-24 and Praziquantel and still perform the analysis of the fragmentation of genomic DNA in situ, determination of production superoxide anion, analysis of the expression of transcripts for the anti-apoptotic genes and pro-apoptotic and determining the enzymatic activity of antioxidant enzymes Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) Glutathione Reductase (GR) and Glutathione S Transferase (GST). Seeking to better understand the parasite's biology, and to understand the mechanism of action of EF-24 and praziquantel, in the search for new drugs that are effective against the parasite. (AU)