High throughput screenings: new breeze in anti-Trypanosoma cruzi drug discovery
Julio Alonso-Padilla and Ana Rodríguez
from: Protozoan Parasitism: From Omics to Prevention and Control (Edited by: Luis Miguel de Pablos Torró and Jacob-Lorenzo Morales). Caister Academic Press, U.K. (2018) Pages: 31-48.
Development of therapeutic solutions for Chagas disease, which is caused by the protozoan Trypanosoma cruzi, has been historically neglected. Despite being the parasitic disease of highest impact in America, there is no vaccine in sight and the only two available drugs for treatment, benznidazole and nifurtimox, display severe toxicity. These drugs have good efficacy against acute T. cruzi infections and are relatively well tolerated by young patients. Nonetheless, the acute stage of the disease is mostly asymptomatic and largely remains undiagnosed and untreated. Cardiac and/or digestive life-threatening symptoms arise in the chronic stage, which is when diagnosis is generally achieved. At this stage, the efficacy of current drugs is diminished and their side effects prompt to ~20% of treatment discontinuation. Thus there is an urgent need for more efficacious and less toxic therapies for the estimated 7 million chronically infected patients. To meet this challenge, massive screenings have been recently performed over large chemical collections to identify new chemical structures fitted with anti-T. cruzi specific activity. The parasite´s biological complexity and the lack of detailed metabolic and biochemical information have favored a phenotypic over a target-based drug discovery strategy. The first fruits of these high throughput screening campaigns are now arriving at the pre-clinical steps of the drug developmental pathway read more ...