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Mechanisms of action of lysophospholipid analogues against trypanosomatid parasites.

Abstract：

:Lysophospholipid analogues (LPAs) comprise a class of metabolically stable compounds that have been developed as anticancer agents for over two decades, but which have also potent and selective antiparasitic activity, particularly against trypanosomatid parasites such as Leishmania and Trypanosoma cruzi, both in vitro and in vivo. The in vivo activities of LPAs result from direct effects on their target cells and are not dependent on a functional immune system. Because of their chemical nature, LPAs have a potential for interaction with a variety of subcellular structures and biochemical pathways. However, in mammalian cells LPA-induced growth inhibition and programmed cell death is usually associated with a blockade of phosphatidylcholine (PC) biosynthesis at the level of CTP: phosphocholine citidyltransferase, probably through an increase of cellular ceramide levels due to depressed sphingomyelin synthesis. Although in trypanosomatid parasites much less information is available, inhibition of PC biosynthesis by LPA has also been documented but at the level of phosphatidylethanolamine N-methyl-transferase, as well as LPA-induced classical apoptotic phenomena. The higher activity of LPAs as inhibitors of PC biosynthesis in parasites than in mammalian cells, probably due to different biochemical pathways involved in the two types of cells, could explain their selective antiparasitic action in vivo.

journal_name

Trans R Soc Trop Med Hyg

journal_title

Transactions of the Royal Society of Tropical Medicine and Hygiene

authors

Urbina JA

doi

10.1016/j.trstmh.2006.03.010

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

S9-S16

eissn

0035-9203

issn

1878-3503

pii

S0035-9203(06)00210-0

journal_volume

100 Suppl 1

pub_type

杂志文章,评审

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