Back to Search
Start Over
Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids
- Source :
- European Journal of Medicinal Chemistry. 133:319-328
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo. The most potent compound, 5c, arrested HepG2 cells (IC50 = 4.23 ± 0.79 μM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies.
- Subjects :
- G2 Phase
0301 basic medicine
Antineoplastic Agents
Apoptosis
Chromosomal translocation
01 natural sciences
Cinnamic acid
Mice
03 medical and health sciences
chemistry.chemical_compound
In vivo
Drug Discovery
Animals
Humans
Benzopyrans
Protein kinase B
Pharmacology
Esterification
Low toxicity
Caspase 3
010405 organic chemistry
Liver Neoplasms
Organic Chemistry
Bergenin
Hep G2 Cells
General Medicine
Caspase 9
In vitro
0104 chemical sciences
030104 developmental biology
Liver
Proto-Oncogene Proteins c-bcl-2
chemistry
Biochemistry
Cinnamates
Female
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 133
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....98ef3798a41cef356794e415ba428b93