RRC ID 65143
著者 El-Naggar MH, Mira A, Abdel Bar FM, Shimizu K, Amer MM, Badria FA.
タイトル Synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy.
ジャーナル Bioorg Med Chem
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; 1.54μM). 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 15.24μM, respectively. Meanwhile, methyl shogoal (D8) and 4'-O-prenyl-[6]-gingerol (D10) retained the highest inhibition with IC50; 4.92 and 3.01μM, for aminopeptidase, and 11.27 and 7.25μM for epoxide hydrolase activities, respectively.
巻・号 25(3)
ページ 1277-1285
公開日 2017-2-1
DOI 10.1016/j.bmc.2016.12.048
PII S0968-0896(16)31149-X
PMID 28065501
MeSH Aminopeptidases / antagonists & inhibitors Aminopeptidases / metabolism Antineoplastic Agents / chemical synthesis Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Catechols / chemical synthesis Catechols / chemistry Catechols / pharmacology* Cell Proliferation / drug effects Colorectal Neoplasms / drug therapy* Colorectal Neoplasms / metabolism Colorectal Neoplasms / pathology Dose-Response Relationship, Drug Enzyme Inhibitors / chemical synthesis Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology* Epoxide Hydrolases / antagonists & inhibitors* Epoxide Hydrolases / metabolism Fatty Alcohols / chemical synthesis Fatty Alcohols / chemistry Fatty Alcohols / pharmacology* Humans Molecular Docking Simulation* Molecular Structure Recombinant Proteins / metabolism Structure-Activity Relationship Tumor Cells, Cultured
IF 3.073
リソース情報
ヒト・動物細胞 HF19(RCB0210)