Synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy

Mai H. El-Naggar, Amira Mira, Fatma M. Abdel Bar, Kuniyoshi Shimizu, Mohamed M. Amer, Farid A. Badria

研究成果: Contribution to journalArticle査読

23 被引用数 (Scopus)


Leukotriene A4 hydrolase (LTA4H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene which may play an important role in chronic inflammation associated carcinogenesis. [6]-gingerol, the major bioactive compound of Zingiber officinale, is a potential inhibitor of LTA4H, a highly expressed enzyme in colorectal carcinoma. Eighteen compounds; seven of natural origin (including [4]-, [6]-, [8]-, and [10]-gingerol), five new and six known semi-synthesized [6]-gingerol derivatives were examined using docking, in vitro cytotoxicity against human colon cancer cells (HCT-116) and LTA4H aminopeptidase and epoxide hydrolase inhibitory studies. Methyl shogoal (D8) showed to be the most potent compound against HCT-116 cells (IC50; 1.54 μM). Remarkably, D8 proved to be non-cytotoxic to normal cells; (TIG-1) and (HF-19) with high selective index (SI; 52.3). Furthermore [6]-gingerol derivatives showed potent LTA4H inhibitory activities in comparison to the universal positive controls (bestatin and 4BSA). Among the natural gingerols, [10]-gingerol (N3) exhibited the highest LTA4H aminopeptidase and epoxide hydrolase inhibitory activities with IC50; 21.59 and 15.24 μM, respectively. Meanwhile, methyl shogoal (D8) and 4′-O-prenyl-[6]-gingerol (D10) retained the highest inhibition with IC50; 4.92 and 3.01 μM, for aminopeptidase, and 11.27 and 7.25 μM for epoxide hydrolase activities, respectively.

ジャーナルBioorganic and Medicinal Chemistry
出版ステータス出版済み - 1 1 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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