Descubrimiento de nuevas moléculas activas frente a Typanasoma cruzi y Leishmania donovani

Resumo

Visceral leishmaniasis (VL) and Chagas disease (CD), caused by kinetoplastid parasites, affectmillions of people worldwide and impart a heavy burden against human health. Due to thelimited efficacy and toxicity related effects of the existing treatments, there is an urgent needto develop novel therapies with superior efficacy and safety profiles to successfully treat thesediseases. There are several strategies available with the aim of finding novel therapies againstLeishmania and Trypanosoma cruzi: the discovery of novel molecules by de novo screening ofcompound libraries, combination therapies, the development of novel formulations for alreadyknown drugs, and drug repurposing.The main focus of this thesis is the strategy based on de novo screening of Calibr 150 000compound library against the parasites Leishmania donovani, as a causative agent of VL, andTrypanosoma cruzi, that causes CD. With this objective, a progression cascade was designed foreach parasite, starting with the higher throughput assays and establishing, later on, the mostrelevant biological assays as secondary assays...