Design and synthesis of potent antileishmanial cycloalkylidene-substituted ether phospholipid derivatives

Calogeropoulou, T; Angelou, P; Detsi, A; Fragiadaki, I; Scoulica, E

dc.contributor.author	Calogeropoulou, T	en
dc.contributor.author	Angelou, P	en
dc.contributor.author	Detsi, A	en
dc.contributor.author	Fragiadaki, I	en
dc.contributor.author	Scoulica, E	en
dc.date.accessioned	2014-03-01T01:28:07Z
dc.date.available	2014-03-01T01:28:07Z
dc.date.issued	2008	en
dc.identifier.issn	00222623	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/18715
dc.subject.other	antileishmanial agent	en
dc.subject.other	cyclopentadecylpentylphosphocholine	en
dc.subject.other	ether phospholipid	en
dc.subject.other	miltefosine	en
dc.subject.other	piperidine derivative	en
dc.subject.other	trimethylammonium salt derivative	en
dc.subject.other	unclassified drug	en
dc.subject.other	amastigote	en
dc.subject.other	article	en
dc.subject.other	controlled study	en
dc.subject.other	cytotoxicity	en
dc.subject.other	drug activity	en
dc.subject.other	drug design	en
dc.subject.other	drug synthesis	en
dc.subject.other	hemolysis	en
dc.subject.other	human	en
dc.subject.other	human cell	en
dc.subject.other	hydrogenation	en
dc.subject.other	IC 50	en
dc.subject.other	Leishmania infantum	en
dc.subject.other	leishmaniasis	en
dc.subject.other	macrophage	en
dc.subject.other	monocyte	en
dc.subject.other	Animals	en
dc.subject.other	Cells, Cultured	en
dc.subject.other	Cycloparaffins	en
dc.subject.other	Drug Design	en
dc.subject.other	Ethers	en
dc.subject.other	Hemolysis	en
dc.subject.other	Humans	en
dc.subject.other	Leishmania	en
dc.subject.other	Leishmania donovani	en
dc.subject.other	Leishmania infantum	en
dc.subject.other	Phosphorylcholine	en
dc.subject.other	Structure-Activity Relationship	en
dc.subject.other	Trypanocidal Agents	en
dc.title	Design and synthesis of potent antileishmanial cycloalkylidene-substituted ether phospholipid derivatives	en
heal.type	journalArticle	en
heal.identifier.primary	10.1021/jm701166b	en
heal.identifier.secondary	http://dx.doi.org/10.1021/jm701166b	en
heal.publicationDate	2008	en
heal.abstract	Two series of novel ether phospholipids (EPs) have been synthesized. The first includes cyclodecylidene-or cyclopentadecylidene-substituted EPs carrying N,N,N-trimethylammonium or N-methylpiperidino or N-methylmorpholino head groups. The second series encompasses more rigid head groups in combination with cycloalkylidene moieties in the lipid portion. In addition, hydrogenated derivatives were obtained. All the new analogues, except 33, were 1.5- to 62-fold more potent than miltefosine against the intracellular L. infantum, and the most active ones were also less cytotoxic against the human monocytic cell line THP1 and less hemolytic than miltefosine. The analogues that combine high potency with low cytotoxicity and hemolytic activity were 19, 37, 21 23, 38, 39, and 40. Cyclopentadecylpentylphosphocholine (38) possesses an IC50 of 0.7 μM against L. infantum amastigotes and is the least cytotoxic analogue, since it does not present toxicity against THP1 macrophages, even at a concentration that is 800-fold the antiparasitic IC50 value, and does not present significant hemolytic activity. © 2008 American Chemical Society.	en
heal.journalName	Journal of Medicinal Chemistry	en
dc.identifier.doi	10.1021/jm701166b	en
dc.identifier.volume	51	en
dc.identifier.issue	4	en
dc.identifier.spage	897	en
dc.identifier.epage	908	en