Design, Synthesis, and Biological Activity of Hydrogen Peroxide Responsive Arylboronate Melatonin Hybrids.
Boronic Acids
/ chemical synthesis
Cell Death
/ drug effects
Cell Survival
/ drug effects
Cells, Cultured
Drug Design
HeLa Cells
Humans
Hydrogen Peroxide
/ chemical synthesis
Melatonin
/ chemical synthesis
Molecular Structure
NF-E2-Related Factor 2
/ metabolism
Oxidative Stress
/ drug effects
Reactive Oxygen Species
/ metabolism
Journal
Chemical research in toxicology
ISSN: 1520-5010
Titre abrégé: Chem Res Toxicol
Pays: United States
ID NLM: 8807448
Informations de publication
Date de publication:
22 01 2019
22 01 2019
Historique:
pubmed:
19
12
2018
medline:
20
12
2019
entrez:
19
12
2018
Statut:
ppublish
Résumé
Stimulus-responsive cleavage reactions have found broad use to direct drug release at a particular target disease area. Increased levels of reactive oxygen species (ROS) have been associated with the development and progression of cancer and several other disease states, motivating the development of drug conjugates that can undergo a chemoselective ROS-triggered release. Melatonin (MLT) and the reactive electrophile p-benzoquinone methide ( p-QM) have evidenced either cytoprotective or cytotoxic effects in biological systems, depending on the dose, cellular targets, and time of exposure. In this study, we report the synthesis and biological activity of two MLT derivatives linked to ROS-responsive arylboronate triggers (P1 and P2), which can be activated by endogenously generated hydrogen peroxide (H
Identifiants
pubmed: 30560658
doi: 10.1021/acs.chemrestox.8b00216
doi:
Substances chimiques
Boronic Acids
0
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
Reactive Oxygen Species
0
Hydrogen Peroxide
BBX060AN9V
Melatonin
JL5DK93RCL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM