PUBLICATION
Design, Synthesis, Biological Evaluation, and Preliminary Mechanistic Study of a Novel Mitochondrial-Targeted Xanthone
- Authors
- Wang, S., Zhang, Q., Peng, M., Xu, J., Guo, Y.
- ID
- ZDB-PUB-230212-39
- Date
- 2023
- Source
- Molecules 28(3): (Journal)
- Registered Authors
- Keywords
- antitumor activity, apoptosis, mitochondrial targeting, triphenylphosphonium, zebrafish, α-mangostin
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Antineoplastic Agents*
- Reactive Oxygen Species/metabolism
- Cell Proliferation
- Mitochondria/metabolism
- Xanthones*/metabolism
- Xanthones*/pharmacology
- Zebrafish/metabolism
- Apoptosis
- PubMed
- 36770683 Full text @ Molecules
Citation
Wang, S., Zhang, Q., Peng, M., Xu, J., Guo, Y. (2023) Design, Synthesis, Biological Evaluation, and Preliminary Mechanistic Study of a Novel Mitochondrial-Targeted Xanthone. Molecules. 28(3):.
Abstract
α-Mangostin, a natural xanthone, was found to have anticancer effects, but these effects are not sufficient to be effective. To increase anticancer potential and selectivity, a triphenylphosphonium cation moiety (TPP) was introduced to α-mangostin to specifically target cancer cell mitochondria. Compared to the parent compound, the cytotoxicity of the synthesized compound 1b increased by one order of magnitude. Mechanistic analysis revealed that the anti-tumor effects were involved in the mitochondrial apoptotic pathway by prompting apoptosis and arresting the cell cycle at the G0/G1 phase, increasing the production of reactive oxygen species (ROS), and reducing mitochondrial membrane potential (Δψm). More notably, the antitumor activity of compound 1b was further confirmed by zebrafish models, which remarkably inhibited cancer cell proliferation and migration, as well as zebrafish angiogenesis. Taken together, our results for the first time indicated that TPP-linked 1b could lead to the development of new mitochondrion-targeting antitumor agents.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping