Synthesis, in vitro anti-inflammatory and cytotoxic evaluation, and mechanism of action studies of 1-benzoyl-β-carboline and 1-benzoyl-3-carboxy-β-carboline derivatives

Mei Lin Yang, Ping Chung Kuo, Tsong Long Hwang, Wen Fei Chiou, Keduo Qian, Chin Yu Lai, Kuo Hsiung Lee, Tian Shung Wu

研究成果: Article同行評審

39 引文 斯高帕斯(Scopus)

摘要

In the present study, various 1-substituted and 1,3-disubstituted β-carboline derivatives were synthesized by a modified single-step Pictet-Spengler reaction. The compounds were examined for cytotoxicity and anti-inflammatory activity, as measured by the inhibition of prostaglandin E 2 (PGE 2) production and nitric oxide (NO) production. While only two compounds (28 and 31) showed marginal cytotoxicity against four human cancer cell lines, most of the tested compounds exhibited potent inhibitory activity of both NO and PGE 2 production. Moreover, compounds 6 and 16 significantly reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), suggesting that β-carboline analogs can inhibit NO and PGE 2 production at the translational level. In addition, several of the β-carboline derivatives (1, 2, 4-8, 11, 13, 22, 25, 27, 31, and 41-43) displayed significant inhibitory activity of superoxide anion (O2·-) generation or elastase release compared to the reference compound, with 6 being the most potent. N-Formyl-l-methionyl-phenylalanine (FMLP)-induced phosphorylation of c-Jun N-terminal kinase (JNK) and protein kinase B (AKT) were also inhibited by 6, suggesting that it suppresses human neutrophil functions by inhibiting the activation of JNK and AKT signaling pathways. Therefore, the synthetic 1-benzoyl-3-carboxy β-carboline analogs may have great potential to be developed as anti-inflammatory agents.

原文English
頁(從 - 到)1674-1682
頁數9
期刊Bioorganic and Medicinal Chemistry
19
發行號5
DOIs
出版狀態Published - 2011 3月 1

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子醫學
  • 分子生物學
  • 藥學科學
  • 藥物發現
  • 臨床生物化學
  • 有機化學

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