Trypanosoma cruzi is the causative agent of Chagas disease, a neglected infection affecting millions of people in tropical regions. There are several chemotherapeutic agents for the treatment of this disease, but most of them are inefficient and highly toxic. Natural products have traditionally been a rich source for the discovery of new lead substances and, therefore, the approach of testing those "active ingredients" has been implemented also in discovering anti-parasitic drugs. In the present project, we will perform pharmaceutical studies in order to optimize, lead compounds previously discovered from marine microorganisms. Because the remarkable properties of gallinamide as T. cruci parasiticidal and as inhibitor of cruzipain enzyme, preclinical assays will also be performed with this compound. In addition, other lead compounds such as polyketide and steroid derivatives will be tested against cruzain and T. cruzi both in vitro and in vivo. Furthermore, the pharmacokinetics, pharmacodynamics and liver metabolism of these compounds will be assessed in order to evaluated the drug stability. Finally, with the aid of animal models of Chagas disease we intend to optimize the compounds having the lowest acute toxicity profiles. These experiments will provide insights into the design of novel anti-Chagas drugs.
News published in Agência FAPESP Newsletter about the scholarship: