Synthesis of novel methyl jasmonate derivatives and evaluation of their biological activity in various cancer cell lines.
Acetates
/ chemistry
Antineoplastic Agents
/ chemical synthesis
Cyclopentanes
/ chemistry
Glucose
/ metabolism
Glycolysis
Hexokinase
/ antagonists & inhibitors
Humans
Mitochondria
/ drug effects
Neoplasms
/ drug therapy
Oxylipins
/ chemistry
Phosphorylation
Tumor Cells, Cultured
Voltage-Dependent Anion Channel 1
/ antagonists & inhibitors
Aerobic glycolysis
Cancer therapy
Hexokinase-II inhibition
Methyl jasmonate
Novel drug discovery and development
Warburg effect
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
24
04
2019
revised:
19
07
2019
accepted:
22
07
2019
pubmed:
5
8
2019
medline:
21
10
2020
entrez:
5
8
2019
Statut:
ppublish
Résumé
Warburg hypothesized that the energy consumption of cancer cells is different than the normal cells. When compared to normal conditions, cancer cells do not undergo tricarboxylic acid (TCA) cycle therefore resulting in more lactate in the cells. Glycolysis pathway is a way of cancer cells to provide energy. The first step in glycolysis is the phosphorylation of glucose to glucose-6-phosphate. This reaction is catalyzed by the hexokinase-II enzyme (HK-II) which is known to be overexpressed in tumor cells. The feeding of cancer cells can be prevented by inhibiting the hexokinase-II enzyme in the first step of aerobic glycolysis. In literature, Methyl Jasmonate (MJ) is known as a Hexokinase-II inhibitor since it disposes VDAC and HK-II interaction on mitochondrial membrane. In our study, we aimed to increase the activity by synthesizing the novel MJ analogues with appropriate modifications. Here we report Hexokinase-2 enzyme and cell viability study results in different cancer cells. Based on the three different cancer cell lines we investigated, our novel MJ analogues proved to be more potent than the original molecule. Thus this research may provide more efficacious/novel HK-II inhibitors and may shed light to develop new anti-cancer agents.
Identifiants
pubmed: 31377389
pii: S0045-2068(19)30630-3
doi: 10.1016/j.bioorg.2019.103146
pii:
doi:
Substances chimiques
Acetates
0
Antineoplastic Agents
0
Cyclopentanes
0
Oxylipins
0
methyl jasmonate
900N171A0F
Voltage-Dependent Anion Channel 1
EC 1.6.-
Hexokinase
EC 2.7.1.1
Glucose
IY9XDZ35W2
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103146Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.