Synthesis and biological evaluation of phosphate triester alkyl lysophospholipids (ALPs) as novel potential anti-neoplastic agents.
Phosphate triester derivatives of the anti-neoplastic alkyl lysophospholipids (ALP) have been prepared as novel potential therapeutic agents. In particular, simple, symmetrical phosphate triesters have been prepared, using phosphorochloridate chemistry. The compounds have been fully characterized by a range of techniques, and assayed for their inhibition of DNA synthesis by mammalian cells in culture. The compounds are generally inhibitory towards DNA synthesis in the micromolar range. However, the magnitude of the effect varies greatly with the phosphate structure. In particular, there is a clear trend towards decreasing activity with increasing alkyl chain length. Thus, short-chain dialkyl phosphate esters appear more effective than the reference compound hexadecyl phosphatidyl choline.
McGuigan
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C
Welsh School of Pharmacy, University of Wales Cardiff, UK.
Wang
Y
Y
Riley
P A
PA
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005990:Glycerol / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010742:Phospholipid Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D010758:Phosphorus / Q000737:chemistry; D017553:Phosphorus Compounds; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
C092457:3-O-hexadecyl-2-O-methyl-glycerol-1-O-diethylphosphate; C092456:3-O-hexadecyl-2-O-methylglycerol-1-O-dimethylphosphate; D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D017553:Phosphorus Compounds; D014316:Tritium; D010758:Phosphorus; D004247:DNA; C013196:phosphoryl chloride; D005990:Glycerol; D013936:Thymidine