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Pharmacological evaluation of a novel cyclic phosphatidic acid derivative 3-S-cyclic phosphatidic acid (3-S-cPA)
- Source :
- Bioorganic & Medicinal Chemistry. 20:3196-3201
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator possessing cyclic phosphate ring, which is necessary for its specific biological activities. To stabilize cyclic phosphate ring of cPA, we synthesized a series of cPA derivatives. We have shown that racemic 3-S-cPA, with a phosphate oxygen atom replaced with a sulfur atom at the sn-3, was a more effective autotaxin (ATX) inhibitor than cPA. In this study, we showed that racemic 3-S-cPA also had potent biological activities such as inhibition of cancer cell migration, suppression of the nociceptive reflex, and attenuation of ischemia-induced delayed neuronal cell death in the hippocampal CA1. Moreover, we synthesized both enantiomers of palmitoleoyl derivative of 3-S-cPA, and found that the chirality of 3-S-cPA is not involved in ATX inhibition. Based on these findings, racemic 3-S-cPA is suggested as an effective therapeutic compound like cPA.
- Subjects :
- Male
Programmed cell death
Stereochemistry
Clinical Biochemistry
Phospholipid
Phosphatidic Acids
Pharmaceutical Science
Ring (chemistry)
Biochemistry
Fatty Acids, Monounsaturated
chemistry.chemical_compound
Cell Movement
Drug Discovery
Animals
Humans
heterocyclic compounds
Rats, Wistar
Molecular Biology
Neurons
Cell Death
Molecular Structure
Phosphoric Diester Hydrolases
Organic Chemistry
Stereoisomerism
Phosphatidic acid
Phosphate
Rats
chemistry
cardiovascular system
Molecular Medicine
Enantiomer
Autotaxin
Chirality (chemistry)
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....028d1f9e816e2f80459f7023b27b7d3a