2. Academic Validation
  3. Synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy

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

  • Bioorg Med Chem. 2017 Feb 1;25(3):1277-1285. doi: 10.1016/j.bmc.2016.12.048.
Mai H El-Naggar 1,  Amira Mira 2,  Fatma M Abdel Bar 3,  Kuniyoshi Shimizu 4,  Mohamed M Amer 5,  Farid A Badria 6
Affiliations

Affiliations

  • 1 Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Pharmacognosy Department, Faculty of Pharmacy, Sohag University, Sohag, Egypt. Electronic address: mai.h.elnaggar@gmail.com.
  • 2 Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: dramiramera@gmail.com.
  • 3 Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: fatma_maar@yahoo.com.
  • 4 Division of Systematic Forest and Forest Products Sciences, Department of Agro-Environmental Sciences, Faculty of Agriculture, Graduate School of Kyushu University, Japan. Electronic address: shimizukuni@gmail.com.
  • 5 Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: pharmamer_47@yahoo.com.
  • 6 Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: faridbadria@gmail.com.
PMID: 28065501 DOI: 10.1016/j.bmc.2016.12.048
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.

Keywords

Aminopeptidase; Epoxide hydrolase; Gingerols; HCT-116; LTA(4)H; Semi synthesis; Zingiber officinale.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z