Back to Search
Start Over
Design, synthesis and in vitro evaluation of novel ursolic acid derivatives as potential anticancer agents
- Source :
- European Journal of Medicinal Chemistry. 95:435-452
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- A series of novel ursolic acid (UA) derivatives modified at the C-3 and the C-28 positions were designed and synthesized in an attempt to develop potential antitumor agents. The in vitro cytotoxicity were evaluated against five cancer cell lines (MGC-803, HCT-116, T24, HepG2 and A549 cell lines) and a normal cell (HL-7702) by MTT assay. The screening results indicated that some of these target compounds displayed moderate to high levels of antiproliferative activities compared with ursolic acid and 5-fluorouracil (5-FU), and exhibited much lower cytotoxicity than 5-FU, indicating that the targeted compounds had selective and significant effect on the cell lines. The induction of apoptosis and affects on the cell cycle distribution of compound 6r were investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which revealed that the antitumor activity of 6r was possibly achieved through the induction of cell apoptosis by G1 cell-cycle arrest. Western blot and qRT-PCR (quantitative real-time PCR) experiments demonstrated that compound 6r may induce apoptosis through both of intrinsic and extrinsic apoptosis pathway.
- Subjects :
- Intracellular Space
Antineoplastic Agents
Apoptosis
Chemistry Techniques, Synthetic
chemistry.chemical_compound
Ursolic acid
Cell Line, Tumor
Drug Discovery
Humans
MTT assay
Cytotoxicity
Cell Proliferation
Membrane Potential, Mitochondrial
Pharmacology
Chemistry
Cell growth
Cell Cycle
Organic Chemistry
Acridine orange
General Medicine
Cell cycle
Molecular biology
Triterpenes
Staining
Biochemistry
Caspases
Drug Design
Drug Screening Assays, Antitumor
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 95
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....f37480f9e6edf3d8180b9676c3428524