Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid

Renuka Gupte, Anjaih Siddam, Yan Lu, Wei Li, Yuko Fujiwara, Nattapon Panupinthu, Truc Chi Pham, Daniel L. Baker, Abby L. Parrill, Mari Gotoh, Kimiko Murakami-Murofushi, Susumu Kobayashi, Gordon B. Mills, Gabor Tigyi, Duane Miller

Research output: Contribution to journalArticle

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Abstract

Cyclic phosphatidic acid (CPA) is a naturally occurring analog of lysophosphatidic acid (LPA) in which the sn-2 hydroxy group forms a five-membered ring with the sn-3 phosphate. Here, we describe the synthesis of R-3-CCPA and S-3-CCPA along with their pharmacological properties as inhibitors of lysophospholipase D/autotaxin, agonists of the LPA 5 GPCR, and blockers of lung metastasis of B16-F10 melanoma cells in a C57BL/6 mouse model. S-3CCPA was significantly more efficacious in the activation of LPA 5 compared to the R-stereoisomer. In contrast, no stereoselective differences were found between the two isomers toward the inhibition of autotaxin or lung metastasis of B16-F10 melanoma cells in vivo. These results extend the potential utility of these compounds as potential lead compounds warranting evaluation as cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)7525-7528
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number24
DOIs
StatePublished - Dec 15 2010

Fingerprint

Stereoisomerism
Experimental Melanomas
Pharmacology
Neoplasm Metastasis
Lead compounds
Lung
Phosphatidic Acids
Inbred C57BL Mouse
Isomers
Chemical activation
Phosphates
lysophosphatidic acid
3-carba cyclic-phosphatidic acid
Neoplasms
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid. / Gupte, Renuka; Siddam, Anjaih; Lu, Yan; Li, Wei; Fujiwara, Yuko; Panupinthu, Nattapon; Pham, Truc Chi; Baker, Daniel L.; Parrill, Abby L.; Gotoh, Mari; Murakami-Murofushi, Kimiko; Kobayashi, Susumu; Mills, Gordon B.; Tigyi, Gabor; Miller, Duane.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 24, 15.12.2010, p. 7525-7528.

Research output: Contribution to journalArticle

Gupte, R, Siddam, A, Lu, Y, Li, W, Fujiwara, Y, Panupinthu, N, Pham, TC, Baker, DL, Parrill, AL, Gotoh, M, Murakami-Murofushi, K, Kobayashi, S, Mills, GB, Tigyi, G & Miller, D 2010, 'Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 24, pp. 7525-7528. https://doi.org/10.1016/j.bmcl.2010.09.115
Gupte, Renuka ; Siddam, Anjaih ; Lu, Yan ; Li, Wei ; Fujiwara, Yuko ; Panupinthu, Nattapon ; Pham, Truc Chi ; Baker, Daniel L. ; Parrill, Abby L. ; Gotoh, Mari ; Murakami-Murofushi, Kimiko ; Kobayashi, Susumu ; Mills, Gordon B. ; Tigyi, Gabor ; Miller, Duane. / Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 24. pp. 7525-7528.
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