| Author | Menna-Barreto, Rubem Fiqueiredo Sadok | |
| Author | Castro, Solange Lisboa de | |
| Access date | 2017-11-16T14:20:18Z | |
| Available date | 2017-11-16T14:20:18Z | |
| Document date | 2017 | |
| Citation | MENNA-BARRETO, Rubem Figueiredo Sadok; CASTRO, Solange Lisboa de. Clear Shot at Primary Aim: Susceptibility of Trypanosoma cruzi Organelles, Structures and Molecular Targets to Drug Treatment. Current Topics in Medicinal Chemistry, v.17, p.1-23, 2017. | pt_BR |
| ISSN | 1568-0266 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/23219 | |
| Language | eng | pt_BR |
| Publisher | Bentham Science Publishers | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Quimioterapia | pt_BR |
| Subject in Portuguese | Organelas | pt_BR |
| Subject in Portuguese | Microcorpos | pt_BR |
| Subject in Portuguese | Ultraestutura | pt_BR |
| Subject in Portuguese | Ergosterol | pt_BR |
| Title | Clear Shot at Primary Aim: Susceptibility of Trypanosoma cruzi Organelles, Structures and Molecular Targets to Drug Treatment | pt_BR |
| Type | Article | |
| Abstract | Chagas disease, caused by Trypanosoma cruzi, stands out due to its socio-
economic effects on low-income tropical populations. This disease affects millions
of people worldwide. The current chemotherapy for it is based on benznidazole
(Bz) and nifurtimox (Nif) and is unsatisfactory. In this review, we will focus
on the search for potential target organelles and molecules for the chemotherapy of
Chagas disease. We consider as potential target organelles those that are absent or
significantly different in host cells and present in the clinically relevant forms of
the parasite (trypomastigotes and amastigotes), which are the mitochondrion, cytoskeletal-
related structures, the acidocalcisomes/contractile vacuole complex and
glycosomes. Most molecular targets are key enzymes involved in processes that are
essential to parasite survival, such as sterol biosynthesis, antioxidant defences and bioenergetic pathways.
Among the molecular targets, enzymes of the sterol pathway, particularly C14α-sterol demethylase,
are still the most promising target, even if clinical trials with posaconazole and E1224 have
failed to sustain efficacy. We believe that in the near future, the Chagas community will have a “clear
shot” at new drug candidates for Chagas disease based on the accumulated knowledge about trypanosomatid
biochemistry, preclinical studies, advances in screening technologies, the efforts of medicinal
chemists in the synthesis of both azolic and non-azolic inhibitors, and the interest of pharmaceutical
companies in the development of new antifungal agents, which form a critical mass of information. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Chagas Disease | pt_BR |
| Subject | chemotherapy | pt_BR |
| Subject | drug targets | pt_BR |
| Subject | Organelles | pt_BR |
| Subject | glycosomes | pt_BR |
| Subject | Ultrastructure | pt_BR |
| Subject | Ergosterol biosynthesis pathway | pt_BR |
| Subject | Acidocalcisome-contractile vacuole complex | pt_BR |
| Subject | molecular targets | pt_BR |
| Subject | Cytoskeletal- related structures | pt_BR |
| Subject | mitochondrion-kinetoplast | pt_BR |
| e-ISSN | 1873-4294 | |
| Embargo date | 2030-01-01 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
