| Full text | |
| Author(s): |
Balanco, Jose Mario F.
[1]
;
Sussmann, Rodrigo A. C.
[1]
;
Verdaguer, Ignasi B.
[1]
;
Gabriel, Heloisa B.
[1]
;
Kimura, Emilia A.
[1]
;
Katzin, Alejandro M.
[1]
Total Authors: 6
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Av Lineu Prestes 1374, BR-05508000 Sao Paulo, SP - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | FEBS OPEN BIO; v. 9, n. 4, p. 743-754, APR 2019. |
| Web of Science Citations: | 1 |
| Abstract | |
Leishmaniasis is a neglected disease caused by a trypanosomatid protozoan of the genus Leishmania. Most drugs used to treat leishmaniasis are highly toxic, and the emergence of drug-resistant strains has been observed. Therefore, new therapeutic targets against leishmaniasis are required. Several isoprenoid compounds, including dolichols or ubiquinones, have been shown to be important for cell viability and proliferation in various trypanosomatid species. Here, we detected the biosynthesis of tocopherol in Leishmania (L.) amazonensis promastigotes invitro through metabolic labelling with {[}1-(n)-3H]-phytol. Subsequently, we confirmed the presence of vitamin E in the parasite by gas chromatography-mass spectrometry. Treatment with usnic acid or nitisinone, inhibitors of precursors of vitamin E synthesis, inhibited growth of the parasite in a concentration-dependent manner. This study provides the first evidence of tocopherol biosynthesis in a trypanosomatid and suggests that inhibitors of the enzyme 4-hydroxyphenylpyruvate dioxygenase may be suitable for use as antileishmanial compounds. (AU) | |
| FAPESP's process: | 17/22452-1 - Biosynthesis of isoprenoids in Plasmodium falciparum: evaluation of possible targets to obtain new anti-malarial drugs |
| Grantee: | Alejandro Miguel Katzin |
| Support Opportunities: | Research Projects - Thematic Grants |