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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1277-1285
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number3
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Cytotoxicity
Colorectal Neoplasms
Derivatives
Epoxide Hydrolases
Aminopeptidases
Inhibitory Concentration 50
HCT116 Cells
Therapeutics
Leukotrienes
Ginger
Enzymes
leukotriene A4 hydrolase
gingerol
Colonic Neoplasms
Cells
Carcinogenesis
Inflammation

All Science Journal Classification (ASJC) codes

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

Cite this

Synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy. / El-Naggar, Mai H.; Mira, Amira; Abdel Bar, Fatma M.; Shimizu, Kuniyoshi; Amer, Mohamed M.; Badria, Farid A.

In: Bioorganic and Medicinal Chemistry, Vol. 25, No. 3, 01.01.2017, p. 1277-1285.

Research output: Contribution to journalArticle

El-Naggar, Mai H. ; Mira, Amira ; Abdel Bar, Fatma M. ; Shimizu, Kuniyoshi ; Amer, Mohamed M. ; Badria, Farid A. / Synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy. In: Bioorganic and Medicinal Chemistry. 2017 ; Vol. 25, No. 3. pp. 1277-1285.
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