ChemInform Abstract: Novel Esters and Amides of Nonsteroidal Antiinflammatory Carboxylic Acids as Antioxidants and Antiproliferative Agents

Autor: Jon C. Nixon, Karen S. Haggard, Mark R. Hellberg, Abdelmoula Namil, Karen C. David, Pete Delgado, Gustav Graff, Timothy L. Kessler
Rok vydání: 2010
Předmět:
Zdroj: ChemInform. 30
ISSN: 1522-2667
0931-7597
Popis: A series of phenolic antioxidant ester and amide derivatives of the nonsteroidal antiinflammatory drug naproxen was designed to have both antiinflammatory and cytoprotective activity. Compounds were evaluated in vitro both for antioxidant activity, as assessed indirectly by thiobarbituric acid reactive substance (TBARS) formation in a membrane lipid peroxidation assay, and for antiproliferative activity, as indexed by the inhibition of DNA synthesis in cultured human vascular endothelial cells. Compounds of this series exhibited potent antioxidant activity, with IC50 values (1.6−11.63 μM) 2−6-fold lower than that of Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) and 400−1300-fold lower than that of vitamin E. Structural modifications of the ester or amide substructure (5a and 6a) did not affect antioxidant activity, but methylation of the 6-hydroxy substituent resulted in compound 6f which was devoid of antioxidant activity. Although indistinguishable in antioxidant activity, the amide de...
Databáze: OpenAIRE
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