학술논문
Oleanolic acid oxime derivatives and their conjugates with aspirin modulate the NF-κB-mediated transcription in HepG2 hepatoma cells.
Document Type
Academic Journal
Author
Krajka-Kuźniak V; Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland.; Bednarczyk-Cwynar B; Department of Organic Chemistry Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.; Paluszczak J; Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland.; Szaefer H; Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland.; Narożna M; Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland.; Zaprutko L; Department of Organic Chemistry Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.; Baer-Dubowska W; Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznan, Poland. Electronic address: baerw@ump.edu.pl.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE
Subject
Language
English
Abstract
The aim of this study was to evaluate the effect of new oleanolic acid oxime (OAO) derivatives and their conjugates with aspirin (ASP) on the expression and activation of NF-κB in human hepatoma HepG2 cells. OAO derivatives showed a stronger cytotoxic effect against HepG2 cells compared with their conjugates with aspirin. Moreover, conjugation of OAO with ASP led to enhanced downregulation of NF-κB expression and activation. Among the hybrids with ASP, compounds: 19, 3-(2-acetoxy)benzoyloxyiminoolean-12-en-28-oic acid morpholide and 13, 3-(2-acetoxy)benzoyloxyiminoolean-12-en-28-oic acid methyl ester, differing, respectively, in morpholide and methyl ester groups at the C-17 position of oleanolic acid (OA) molecule were the most efficient. COX-2 transcript and protein levels were also diminished after treatment with these compounds. The results of this study indicate that the new derivatives of OAO and particularly their conjugates with ASP, downregulate the expression of COX-2 in HepG2 cells by modulating the NF-κB signaling pathway and suggest their potential application in the prevention of liver inflammation and cancer.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
(Copyright © 2019 Elsevier Inc. All rights reserved.)