Synthesis of alkyl chain-modified ether lipids and evaluation of their in vitro cytotoxicity
| Autor: | Romolo A. Gambetta, Nuria Suesa, Cinta Lobato, Liset Borras, Patrizia Banfi, Empar Fos, David Mauleón, Germano Carganico, Franco Zunino |
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| Rok vydání: | 1995 |
| Předmět: |
Chemical Phenomena
Stereochemistry Cell Survival Ether In Vitro Techniques Chemical synthesis Hemolysis chemistry.chemical_compound Structure-Activity Relationship Stereospecificity Drug Discovery medicine Tumor Cells Cultured Animals Humans Platelet Activating Factor Cytotoxicity Alkyl chemistry.chemical_classification Chemistry Physical medicine.disease In vitro Growth Inhibitors chemistry Biochemistry Molecular Medicine Stereoselectivity Rabbits Lysophospholipids Cell Division |
| Zdroj: | Journal of medicinal chemistry. 38(7) |
| ISSN: | 0022-2623 |
| Popis: | A series of alkyl lysophospholipid (ALP) analogs of ET-18-OCH 3 (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) containing modifications in the long C-1 chain has been synthesized and evaluated in human tumor cell line cytotoxicity assays. The compounds have also been evaluated in platelet activating factor (PAF) receptor agonism and hemolysis tests. Two modifications have been studied, introduction of a carbonyl group at different positions of the C-1 chain and branching of this chain, in some compounds with incorporation of a phenyl group. Several compounds showed a cytotoxic potency comparable to that of the reference compound ET-18-OCH 3 , associated with reduced proaggregating and hemolytic effects. The two enantiomers of 1-O-(7-oxooctadecyl)-2-O-methyl-rac-glycero-3-phosphocholine (2) showed the same level of cytotoxicity or antiproliferative activity, with the PAF-agonistic effect confined to R-2. The very low stereoselectivity found in the in vitro cytotoxicity confirms earlier results and indicates a lack of stereospecific interactions with a macromolecular target |
| Databáze: | OpenAIRE |
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