Mechanisms underlying molecules exhibiting anti-Trypanosoma cruzi activity in vitro

Benznidazol and nifurtimox are the unique drugs to have trypanocidal effects which are used to treat Chagasic patients although both of then exhibit considerable cytotoxicity. Therefore, there is a need for continued investigation into molecules that are more effective against T. cruzi and have fewer adverse effects. The aim of this study is to review the described mechanisms of action as well as the physicochemical properties of molecules with anti-Trypanosoma cruzi activity in vitro. Studies available on PubMed and LILACS, describing the mechanism of action of molecules tested in vitro against T. cruzi published from 2003 to May 2023, were evaluated. The Chemicalize.org platform was used to estimate the physicochemical characteristics of the molecules. A total of 188 molecules with described mechanisms of action was reviwed. Among these mechanisms, the primary one described was the alteration of oxidative metabolism, reported as both a direct action on the mitochondria and the inhibition of key enzymes in this process, such as trypanothione reductase, iron superoxide dismutase, and mitochondrial dehydrogenase. Other mechanisms identified included morphological alterations, inhibition of sterol synthesis, and DNA damage. Understanding the molecular pathways involved in drug action enables the targeted search for more effective and less cytotoxic molecules. The molecules studied have great potential for the development of new medicines, due to their promising chemical characteristics, highlighting the importance of continuing studies in this field.