| Structure-activity relationship of salicylic acid derivatives on inhibition of TNF-α dependent NFκB activity: Implication on anti-inflammatory effect of N-(5-chlorosalicyloyl)phenethylamine against experimental colitis. | |
| | |
MedLine Citation:
|
PMID: 22154834 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
To develop a more potent NFκB inhibitor from salicylic acid which is known to inhibit activity of NFκB, a transcription factor regulating genes involved in immunity, inflammation and tumorigenesis, derivatives of salicylic acid (SA) where the 5 position, carboxyl or hydroxyl group was modified were treated in HCT116 cells transfected with an NFκB dependent luciferase gene and LPS-stimulated RAW264.7 cells. Amidation of the carboxylic group or substitution of chlorine at the 5 position increased the ability of SA to suppress the expression of NFκB dependent luciferase and inducible nitric oxide synthase, a product of an NFκB target gene. Moreover, simultaneous amidation and chlorination of SA (5-chlorosalicylamide; 5-CSAM) conferred an additive NFκB inhibitory activity on SA. To further enhance the inhibitory activity, N-modification was imposed on 5-CSAM. N-(5-chlorosalicyloyl)phenethylamine (5-CSPA), N-(5-chlorosalicyloyl)3-phenylpropylamine (5-CSPPA) and N-(5-chlorosalicyloyl)4-hydroxyphenylethylamine (5-CSHPA) showed greater potencies for inhibiting NFκB activity than other derivatives. Their IC(50)s' in the luciferase assay measured 15μM (5-CSPA), 17μM (5-CSPPA) and 91μM (5-CSHPA). Rectal administration of 5-CSPA ameliorated TNBS-induced rat colitis, which was more effective than a conventional drug, 5-aminosalicylic acid. These data may provide useful information for development of a therapeutic agent for treatment of diseases where NFκB plays a critical role in the pathogenic progresses. |
| | |
Authors:
|
Jihye Kim; Sookjin Kang; Sungchae Hong; Soowhan Yum; Young Mi Kim; Yunjin Jung |
Related Documents
:
|
6115674 - The effect of essential amino acid deprivation on poly(a) metabolism in neurospora crassa. 1554164 - The effects of different phosphoric acid concentrations on surface enamel. 12001244 - Dentin proteoglycans: an immunocytochemical feisem study. 9821674 - Formation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) by pha synthase from ralston... 12633884 - Effects of aniracetam on extracellular levels of transmitter amino acids in the hippoca... 7921174 - Comparative and optimized dabsyl-amino acid analysis of synthetic phosphopeptides and g... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-11-25 |
Journal Detail:
|
Title: European journal of medicinal chemistry Volume: - ISSN: 1768-3254 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
|
Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0420510 Medline TA: Eur J Med Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 Elsevier Masson SAS. All rights reserved. |
Affiliation:
|
Laboratory of Biomedicinal Chemistry, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Synthesis and in vitro antimycobacterial activity of compounds derived from (R)- and (S)-2-amino-1-...
Next Document: Synthesis, antimicrobial, anticancer evaluation and QSAR studies of 6-methyl-4-[1-(2-substituted-phe...