Accession Number : ADA629508


Title :   Structure-Activity Relationships in the Cytoprotective Effect of Caffeic Acid Phenethyl Ester (CAPE) and Fluorinated Derivatives: Effects on Heme Oxygenase-1 Induction and Antioxidant Activities


Descriptive Note : Journal article


Corporate Author : ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX


Personal Author(s) : Wang, Xinyu ; Stavchansky, Salomon ; Kerwin, Sean M ; Bowman, Phillip D


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a629508.pdf


Report Date : 09 Mar 2010


Pagination or Media Count : 8


Abstract : To determine the relationship between catechol ring modifications and the activity of caffeic acid phenethyl ester (CAPE) as a cytoprotective agent, six catechol ring fluorinated CAPE derivatives were evaluated for their cytoprotective abilities, as well as for their antioxidant and heme oxygenase 1 (HO 1) inducing capacity in a human umbilical vein endothelial cell (HUVEC) model of oxidant stress. To ascertain the involvement of HO 1 induction in the cytoprotective effects of CAPE analogues, their ability to induce HO 1 at 20 M was determined by reverse transcriptase polymerase chain reaction,western blotting and the use of HO 1inhibitor tin protoporphyrin IX. There was significant induction of HO 1 by CAPE derivatives. Inhibition of HO 1 enzymatic activity resulted in reduced cytoprotection. Modi fi cation of the catechol ring of CAPE by introduction of fluorine at various positions resulted in dramatic changes in cytoprotective activity. The maintenance of at least one hydroxyl group on the CAPE catechol ring and the phenethyl ester portion was required for HO 1 induction. CAPE and its derivatives were screened for their ability to scavenge intracellular reactive oxygen species generated in HUVECs by measuring 5 (and 6) chlormethyl 2 ,7 dichlorodihydro fluorescein diacetate oxidation. The maintenance of 3, 4 dihydroxyl groups on the catechol ring was required for antioxidant activity, but antioxidant activity did not guarantee cytoprotection. Methylationor replacement of one hydroxyl group on the catechol ring of CAPE, however, provided both pro oxidant and cytoprotective activities. These results indicate that the induction of HO 1 plays a more important role in the cytoprotective activity of CAPE derivatives tha


Descriptors :   *ANTIOXIDANTS , ACIDS , ASSAYING , CATIONS , CELLS(BIOLOGY) , CHEMICAL AGENTS , CLINICAL MEDICINE , CULTURES(BIOLOGY) , CYTOLOGY , ENDOTHELIUM , ESTERS , FLUORINATION , HEMOGLOBIN , HYDROXYL RADICALS , IN VIVO ANALYSIS , OXIDATION , PHARMACOLOGY , PHYSIOLOGICAL EFFECTS , POLYPHENYLENES , REPRINTS , SYNTHESIS(CHEMISTRY) , TOXICITY


Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE