N,N´-disubstituted diamines as promising anti-trypanosomatids compounds

RECIO-BALSELLS, ALEJANDRO; REIGADA, CHANTAL; LABADIE, GUILLERMO R.; FERREIRA, BIANCA A.; PEREIRA, CLAUDIO A.; COSER, ELIZABETH M.; COELHO, ADRIANO C.

Evento virtual

Congreso; British Society for Parasitology BSP Parasites Online Meeting 2021; 2021

British Society for Parasitology

Our group has synthesized a library of N,N´-disubstituted aliphatic diamines (N,N´-di) that displayed IC50 activities in the µM-nM range against the intracellular and extracellular stages of trypanosomatids parasites (Trypanosoma cruzi-T.c, Leishmania donovani-L.d and Trypanosoma brucei-T.b). Aiming to elucidate the mechanism of action (MoA) of these library, they were evaluated against the Trypanothione synthetase of T.c, T.b and L. infantum-L.i but only displayed low and moderate inhibition (inh10 for L.a., five for L.i and four for L.b (SI= IC50-amast./EC50-BMDM). Compounds L2, L5 and L6, displayed SI>10 for the three species tested (N1,N8-bis(4--(benzyloxy)benzyl)octane-1,8-diamine, SI=15.1-21.5; N1,N12-dibenzyldodecane-1,12-diamine SI=14-22; N1,N12-bis(4-fluorobenzyl)dodecane-1,12-diamine S=19-57).In conclusion, N,N´-di are promising antiparasitic compounds with potent activity against a wide range of Leishmania spp. In addition, part of the MoA could be related to the inhibition of polyamine transport. Considering the previous results on trypanothion synthetase and the results presented here, the MoA of these compounds seems to be polypharmacological, however some relevant target may be involved.