論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | HF19(RCB0210) |