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Sinomenine Derivatives: Synthesis, Antitumor Activity, and Apoptotic Induction in MCF-7 Cells via IL-6/PI3K/Akt/NF-κB Signaling Pathway
- Source :
- ChemMedChem. 17(14)
- Publication Year :
- 2022
-
Abstract
- Natural products have been widely considered as an important resource for new drugs or lead compounds. Sinomenine (SIN) and its derivatives exert antitumor activity via regulation of inflammatory mediators. For these reasons we synthesized three series of SIN derivatives (compounds 4 a-i, 7 a-c and 11 a-c) as antitumor agents from this natural product. All compounds were prepared by modification at the C1 and C4 positions of the A ring, the C4 position of the A ring, and the C6 and C7 positions of the C ring, respectively. All the derivatives were subjected to in vitro antitumor activity against HeLa, A549, HepG-2, MCF-7 and HT-29 cell lines. To observe the apoptotic induction of SIN derivatives and its mechanism, fluorescent staining and western blot assays were carried out for active compound against MCF-7. Based on the screening results, most of the SIN derivatives showed better antitumor activity than SIN. Some of them were found to possess broad-spectrum antitumor activity. Most notably, 11 c exhibited obvious antitumor activity in both cell lines with IC
- Subjects :
- Pharmacology
Molecular Structure
Interleukin-6
Organic Chemistry
NF-kappa B
Antineoplastic Agents
Apoptosis
Biochemistry
Phosphatidylinositol 3-Kinases
Structure-Activity Relationship
Morphinans
Drug Discovery
MCF-7 Cells
Molecular Medicine
Humans
General Pharmacology, Toxicology and Pharmaceutics
Drug Screening Assays, Antitumor
Proto-Oncogene Proteins c-akt
Cell Proliferation
Signal Transduction
Subjects
Details
- ISSN :
- 18607187
- Volume :
- 17
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- ChemMedChem
- Accession number :
- edsair.doi.dedup.....524bc5b97b05ac2ae34f9194a90b2be5