title: Pharmacological evaluation of a novel cyclic phosphatidic acid derivative 3-S-cyclic phosphatidic acid (3-S-cPA).
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.
authors.affiliation: Graduate School of Humanities and Sciences, Department of Life Science, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Nozaki
authors.forename: Mari
authors.initials: M
authors.lastname: Gotoh
authors.forename: Ryo
authors.initials: R
authors.lastname: Tanaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Kato
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakazaki
authors.forename: Harumi
authors.initials: H
authors.lastname: Hotta
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Kimiko
authors.initials: K
authors.lastname: Murakami-Murofushi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects; D010712:Phosphatidic Acids / Q000737:chemistry*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D000099189:Lysophospholipase D
chemical_list: D005229:Fatty Acids, Monounsaturated; D010712:Phosphatidic Acids; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D; C008757:palmitoleic acid