Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid
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 LPA5 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 LPA5 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. © 2010 Elsevier Ltd. All rights reserved.
Bioorganic and Medicinal Chemistry Letters
Gupte, R., Siddam, A., Lu, Y., Li, W., Fujiwara, Y., Panupinthu, N., Pham, T., & Baker, D. (2010). Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid. Bioorganic and Medicinal Chemistry Letters, 20 (24), 7525-7528. https://doi.org/10.1016/j.bmcl.2010.09.115