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

详细信息	查看全文 | 推荐本文 |

• 作者：Emi Nozaki^a ; Mari Gotoh^a ; Ryo Tanaka^b ; Masaru Kato^b ; Takahiro Suzuki^b ; Atsuo Nakazaki^b ; Harumi Hotta^c ; Susumu Kobayashi^b ; Kimiko Murakami-Murofushi^a ; ^{murofushi.kimiko@ocha.ac.jp}
• 关键词：cPA ; cyclic phosphatidic acid ; LPA ; lysophosphatidic acid ; ATX ; autotaxin ; 2ccPA ; 2-O-carba-cyclic phosphatidic acid ; 3ccPA ; 3-O-carba-cyclic phosphatidic acid
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 May, 2012
• 卷：20
• 期：10
• 页码：3196-3201
• 文件大小：637 K

摘要

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.