Synthesis of conjugates of Benznidazol and Proline for evaluation as trypanocidal compounds for Trypanosoma cruzi

TAVERNA PORRO M; SAYÉ M; MIRANDA MR; PEREIRA CA; MOGLIONI AG

Congreso; Drug Discovery for Neglected Diseases International Congress 2018; 2018

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and currently affects 7 million people in Latin America, with almost 70 million more at risk of infection. Nowadays only benznidazole (BZL) and nifurtimox are used to treat this disease, but both present several side effects and are only effective during the chronic stage of the disease. T. cruzi has a metabolism largely based on amino acid consumption, mainly proline (PRO), which can be used as an alternative carbon and energy source to glucose. The parasite T. cruzi presents different transport systems than mammalian cells to uptake amino acids and derivatives from the extracellular medium. For example, the transporter TcAAAP069 is specific for the amino acid L-PRO and it was recently reported that a synthetic proline analogue that inhibits the uptake also possesses trypanocidal effect. The aim of this work is to take advantage of the specificity of TcAAAP069 to direct the entry of BZL into the parasite and to diminish BZL toxicity. In order to do that, we have synthetized a conjugate of BZL and PRO and we are testing their potential as TcAAAP069 inhibitors with trypanocidal action.