title: Dihydrostilbenes and diarylpropanes: Synthesis and in vitro pharmacological evaluation as potent nitric oxide production inhibition agents.
abstract: An efficient synthesis of dihydrostilbenes (1-5) and diarylpropanes (6-10) is achieved from the commercially available starting materials and Wittig-Horner reaction, Claisen-Schmidt condensation and hydrogenation as key steps. Later, their nitric oxide (NO) production inhibition effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages as an indicator of anti-inflammatory activity. All the tested compounds significantly decreased NO production in a concentration-dependent manner except compounds 2, 6 and 8 and did not show notable cytotoxicity except compound 1. Two compounds i.e., compound 9 (hindsiipropane B) (100%; IC50=1.84μM) possessed the most potent NO inhibitory activity which was even stronger than the positive control, L-NMMA (90.1%; IC50=2.73μM) followed by compound 4 (75.5%; IC50=2.98μM) at 10μM concentration and this finding was also further correlated by suppressed expression of LPS stimulated inducible NO synthase. Our study revealed that compound 9, a 1,3-diarylpropane scaffold with 3″,4″-dimethoxyphenyl and 3',4'-dihydroxy-2'-methoxyphenyl motifs could be considered as potential compound or lead compound for further development of NO production-targeted anti-inflammatory agents.
authors: Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon 24252, South Korea.
authors: Ha Young
authors: HY
authors: Jang
authors: Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon 24252, South Korea.
authors: Hyeong Jin
authors: HJ
authors: Park
authors: Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon 24252, South Korea.
authors: Kongara
authors: K
authors: Damodar
authors: Department of Biomedical Science, College of Natural Science, Catholic University of Daegu, Gyeungsan-Si 38430, South Korea.
authors: Jin-Kyung
authors: JK
authors: Kim
authors: Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon 24252, South Korea. Electronic address: jgjun@hallym.ac.kr.
authors: Jong-Gab
authors: JG
authors: Jun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000276:immunology; D011407:Propane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D013267:Stilbenes; D009569:Nitric Oxide; D011407:Propane
keywords: 1,3-Diarylpropanes; Anti-inflammatory; Dihydrostilbenes; Nitric oxide; RAW-264.7 macrophages