Archives of Pharmacal Research

  • 제27권10호
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  • Pages.1053-1059
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  • 2004
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

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)
  • 발행 : 2004.01.01
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초록

$N^1$-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.

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