| Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid. | |
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MedLine Citation:
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PMID: 21051230 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 D Miller |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-08 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 20 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-03-14 Revised Date: 2011-12-19 |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 7525-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Disease Models, Animal Lung Neoplasms / drug therapy, secondary Lysophospholipase / antagonists & inhibitors, metabolism Melanoma, Experimental / pathology Mice Mice, Inbred C57BL Multienzyme Complexes / antagonists & inhibitors, metabolism Phosphatidic Acids / chemical synthesis, chemistry*, pharmacology Phosphodiesterase I / antagonists & inhibitors, metabolism Phosphoric Diester Hydrolases Pyrophosphatases / antagonists & inhibitors, metabolism Receptors, Lysophosphatidic Acid / agonists, metabolism Stereoisomerism |
| Grant Support | |
ID/Acronym/Agency:
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CA92160/CA/NCI NIH HHS; R01 HL079004-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3-carba cyclic-phosphatidic acid; 0/Multienzyme Complexes; 0/Phosphatidic Acids; 0/Receptors, Lysophosphatidic Acid; EC 3.1.1.5/Lysophospholipase; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC 3.1.4.1/Phosphodiesterase I; EC 3.1.4.39/alkylglycerophosphoethanolamine phosphodiesterase; EC 3.6.1.-/Pyrophosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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