Mitochondrial Dysfunction Induced by N-Butyl-1-(4-Dimethylamino)Phenyl-1,2,3,4-Tetrahydro-β-Carboline-3-Carboxamide Is Required for Cell Death of Trypanosoma cruzi.

Background: Chagas' disease is caused by the protozoan Trypanosoma cruzi and affects thousands of people worldwide. The available treatments are unsatisfactory, and new drugs must be developed. Our group recently reported the trypanocidal activity of the synthetic compound N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide (C4), but the mechanism of action of this compound was unclear.

Trypanocidal activity of oxoaporphine and pyrimidine-β-carboline alkaloids from the branches of Annona foetida Mart. (Annonaceae).

Phytochemical investigation of the branches of Annona foetida Mart. led to isolation from the CH(2)Cl(2) extract of four alkaloids: Atherospermidine (1), described for the first time in this species, liriodenine (2), O-methylmoschatoline (3), and annomontine (4). Their chemical structures were established on the basis of spectroscopic data from IR, MS, NMR (1D and 2D), and comparison with the literature.

In vitro and in vivo trypanocidal synergistic activity of N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide associated with benznidazole.

American trypanosomiasis, or Chagas' disease, is caused by Trypanosoma cruzi and affects around 15 million people throughout the American continent. The available treatment is based on two nitroheterocyclic drugs, nifurtimox and benznidazole, both only partially effective and toxic. In this context, new drugs must be found.

Biological activity of 1,2,3,4-tetrahydro-beta-carboline-3-carboxamides against Trypanosoma cruzi.

Several beta-carboline compounds were evaluated for in vitro trypanocidal activity against Trypanosoma cruzi and their potential toxic effects was also assessed. beta-Carboline derivative 4 showed good activity against epimastigote, trypomastigote, and amastigote forms of T. cruzi, with a dose-dependent inhibitory effect.