1. Pharmacological evaluation of a novel cyclic phosphatidic acid derivative 3-S-cyclic phosphatidic acid (3-S-cPA)
- Author
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Emi Nozaki, Ryo Tanaka, Susumu Kobayashi, Atsuo Nakazaki, Harumi Hotta, Kimiko Murakami-Murofushi, Mari Gotoh, Masaru Kato, and Takahiro Suzuki
- 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) - 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.
- Published
- 2012