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Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration
- Source :
- Molecules, Volume 24, Issue 5, Molecules, Vol 24, Iss 5, p 884 (2019)
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- Emodin is a cell arrest and apoptosis-inducing compound that is widely distributed in different plants (rhubarb, aloe), lichens and terrestrial fungi, and also isolated from marine-derived fungi and marine sponge-associated fungi. In this study, we designed and synthesized a novel series of emodin derivatives by binding emodin to an amino acid using linkers of varying lengths and composition, and evaluated their anti-proliferative activities using HepG2 cells (human hepatic carcinoma), MCF-7 cells (human breast cancer) and human normal liver L02 cells. Most of these derivatives showed moderate to potent anti-proliferative activities. Notably, compound 7a exhibited potent anti-proliferative activity against HepG2 cells with the half maximal inhibitory concentration (IC50) value of 4.95 µM, which was enhanced 8.8-fold compared to the parent compound emodin (IC50 = 43.87 µM), and it also exhibited better selective anti-proliferative activity and specificity than emodin. Moreover, further experiments demonstrated that compound 7a displayed a significant efficacy of inducing apoptosis through mitochondrial pathway via release of cytochrome c from mitochondria and subsequent activation of caspase-9 and caspase-3, inducing cell arrest at G0/G1 phase, as well as suppression of cell migration of tumor cells. The preliminary results suggested that compound 7a could be a promising lead compound for the discovery of novel anti-tumor drugs and has the potential for further investigations as an anti-cancer drug.
- Subjects :
- Cell cycle checkpoint
Cell
Pharmaceutical Science
Apoptosis
Analytical Chemistry
chemistry.chemical_compound
0302 clinical medicine
Cell Movement
Neoplasms
Drug Discovery
MCF-7 cells
HepG2 cells
Membrane Potential, Mitochondrial
0303 health sciences
biology
Chemistry
Caspase 3
Cytochrome c
Cell migration
Hep G2 Cells
Cell cycle
Caspase 9
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Biochemistry
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Molecular Medicine
anti-proliferative activity
emodin derivatives
Emodin
Lichens
Article
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
medicine
Humans
Physical and Theoretical Chemistry
Aloe
Rheum
IC50
030304 developmental biology
Cell Proliferation
amino acids
Organic Chemistry
Cell Cycle Checkpoints
biology.protein
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 24
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....506221a4940c3df41e4bde0688fb6d80
- Full Text :
- https://doi.org/10.3390/molecules24050884