Pharmacological evaluation of a novel cyclic phosphatidic acid derivative 3-S-cyclic phosphatidic acid (3-S-cPA)

Bioorg Med Chem. 2012 May 15;20(10):3196-201. doi: 10.1016/j.bmc.2012.03.060. Epub 2012 Apr 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Movement / drug effects
  • Fatty Acids, Monounsaturated / chemistry*
  • Humans
  • Male
  • Molecular Structure
  • Neurons / drug effects
  • Phosphatidic Acids / chemistry*
  • Phosphoric Diester Hydrolases / metabolism
  • Rats
  • Rats, Wistar
  • Stereoisomerism

Substances

  • Fatty Acids, Monounsaturated
  • Phosphatidic Acids
  • palmitoleic acid
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase