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.
N1-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 IC50 value of 9.2 microM, where pyrrolidine dithiocarbamate and parthenolide as positive controls exhibited IC50 values of 29.3 and 3.6 microM, 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-kappaB). Structural analogs of JSH-21 also inhibited both the LPS-induced NO production and NF-kappaB transcriptional activity, where diamine substitution at positions 1 and 2 of JSH-21 seems to play an important role in the anti-inflammatory activity.
Min
Kyung Rak
KR
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Korea. krmin@chungbuk.ac.kr [corrected]
Shin
Hyun-Mo
HM
Lee
Jee-Hyun
JH
Kim
Byung Hak
BH
Chung
Eun Yong
EY
Jung
Sang-Hun
SH
Kim
Youngsoo
Y
D000588:Amines / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D014158:Transcription, Genetic / Q000187:drug effects*
D000588:Amines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001593:Benzyl Compounds; D008070:Lipopolysaccharides; C497734:N1-benzyl-4-methylbenzene-1,2-diamine; D016328:NF-kappa B; D009569:Nitric Oxide; D004247:DNA; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II