Trypanosomatids Metabolic Systems as Potential Chemotherapeutic Targets

Abstract

Trypanosomatids diseases are well known for a long time. These blood-borne parasites peculiarly present vector and host alternating forms with well-differentiated biochemistry, morphology and ways to escape. Recent studies about the metabolic ways used by these parasites are of great scientific interest, especially the divergence of parasite and human host metabolic pathways. Thus, the obtaining of energy (glycolytic pathway), polyamine biosynthesis, sterol biosynthesis, microtubule biosynthesis, folate metabolism, and the DNA topoisomerase, trypanothione redutase, hypoxanthine-guanine phosphoribosyltransferase, nitric oxide synthase, arginase, cysteine protease, and superoxide dismutase enzymes have proved to be important targets to new anti-trypanosomal agents.

Chemistry and Pharmacology of Bergenin or Its Derivatives: A Promising Molecule

“…Growth inhibition is achieved by inhibiting three glycolytic enzymes of the parasite: GAPDH (glyceraldehyde-3-phosphate dehydrogenase), PFK (phosphofructokinase), and PGK (phosphoglycerate kinase), which leads to the death of the parasite. Melos and Echearria [ 110 ] reported that trypanosomatids are highly dependent on glycolysis for ATP production, and, as many glycolytic enzymes have their own characteristics, they are considered to be potential targets for new chemotherapeutic agents.…”

Atividade anti->i<Trypanosoma cruzi >/i<de derivados do 5-nitrofurano e algumas características de seu modo de ação.

“…É importante lembrar que a diferença estrutural entre as tubulinas de parasitos e mamíferos é de aproximadamente 18%. Um possível alvo para fármacos é a γ-tubulina, uma vez que desempenha um importante papel na regulação da nucleação dos microtúbulos e no funcionamento dos flagelos (GULL, 1999;MELOS, ECHEVARRIA, 2012).…”