E-Cyanoacrylamides and 5-Imino Pyrrolones against Trypanosoma cruzi: Activity and Induced Mechanisms of Cell Death

Abstract

Chagas disease is caused by a protozoan parasite called Trypanosoma cruzi. The infection produces a first clinical phase, commonly asymptomatic or showing non-specific symptoms, and a second chronic phase characterized by cardiac and digestive dysfunctions in some individuals with the disease. This disease affects 7 million people and has been categorized by the World Health Organisation as a neglected tropical disease. In addition, the drugs used to combat it were developed in the 1970s and present major toxicity problems and limited efficacy in the chronicity of the disease. This has led to research into new active compounds that are effective against the disease, with studies on cyanoderivatives showing promising activity. In this work, eight active E-cyanoacrylamides/5-imino pyrrolones were studied. Compounds B and F showed excellent activity, while compounds C and G stood out for their lower cytotoxicity. After correlating the activity and cytotoxicity of the compounds, it was observed that compounds B, C, and G obtained the most favourable results. Various cell death studies were carried out with these compounds, and it was determined that all of them produced programmed cell death, with compound B standing out as being at a late stage in the process.