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Anti-Inflammatory Effects of N1-Benzyl-4-Methylbenzene-1,2-Diamine (JSH-21) Analogs on Nitric Oxide Production and Nuclear Factor-kappa B Transcriptional Activity in Lipopolysaccharide-Stimulated Macrophages RAW 264.7  

Min, Kyung-Rak (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
Shin, Hyun-Mo (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
Lee, Jee-Hyun (College of Pharmacy, Chungnam National University)
Kim, Byung-Hak (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
Chung, Eun-Yong (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
Jung, Sang-Hun (College of Pharmacy, Chungnam National University)
Kim , Young-Soo (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
Publication Information
Archives of Pharmacal Research / v.27, no.10, 2004 , pp. 1053-1059 More about this Journal
Abstract
$N^1$-Benzyl-4-methylbenzene-1,2-diamine (JSH-21) and its analogs were chemically synthesized and their anti-inflammatory potentials investigated. JSH-21 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 in a dose-dependent manner, with an $IC_{50}$ value of 9.2 ${\mu}M$, where pyrrolidine dithiocarbamate and parthenolide as positive controls exhibited $IC_{50}$ values of 29.3 and 3.6 ${\mu}M$, respectively. The inhibitory effect of JSH-21 on the NO production was attributable to its down-regulatory action on LPS-inducible NO synthase (iNOS), which was documented by iNOS promoter activity. In the mechanism of the anti-inflammatory action, JSH-21 exhibited inhibitory effects on LPS-induced DNA binding activity and transcriptional activity of nuclear factor-kappa B (NF-$_KB$). Structural analogs of JSH-21 also inhibited both the LPS-induced NO production and NF-$_KB$). transcriptional activity, where diamine substitution at positions 1 and 2 of JSH-21 seems to play an important role in the anti-inflammatory activity.
Keywords
$N^1$-Benzyl-4-methylbenzene-1; 2-diamine; Chemical preparation; Anti-inflammatory effect; Nitric oxide; Nuclear factor-kappa B; Lipopolysaccharide;
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