Document Detail


Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid.
MedLine Citation:
PMID:  21051230     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-08
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  20     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-03-14     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  7525-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
CA92160/CA/NCI NIH HHS; R01 CA092160/CA/NCI NIH HHS; R01 HL079004/HL/NHLBI NIH HHS; R01 HL079004-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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
Comments/Corrections

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