Chagas' disease is a parasitic infection caused by T. cruzi that is currently endemic in Latin America. Current treatments using drugs, nifurtimox and benznidazole are accompanied with a high levels of toxicity. Although vector control and serological screening have significantly reduced the transmission, there is still an urgent demand for effective treatments. Our drug design strategy against Chagas' disease is focused on the dihydrofolate reductase activity of T. cruzi (TcDHFR) as a potential drug target. DHFR catalyzes the reduction of folate to dihydrofolate and to tetrahydrofolate by use of the cofactor NADPH. This biological process is essential for the survival of the parasite. Hence inhibition of TcDHFR is an attractive strategy for the development treatments for Chagas' disease. Our research is focused on developing inhibitors that are selective to TcDHFR compared to hDHFR. Design, synthesis and evaluation of several selective highly potent TcDHFR inhibitors will be presented.

<i>Trypanosoma cruzi</i> dihydrofolate reductase inhibitors: A potential Chagas disease treatment

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Trypanosoma cruzi dihydrofolate reductase inhibitors: A potential Chagas disease treatment