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Synthesis and antiproliferative activity of a natural like glycoconjugate polycyclic compound
- Source :
- European Journal of Medicinal Chemistry. 122:247-256
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- A natural like O -glycoconjugate polycyclic compound 4 was obtained by a multistep procedure starting from N -(3-methyl-1-(4-nitrophenyl)-1 H -pyrazol-5-yl)acetamide. The glycosyl derivative 4 showed antiproliferative activity against all the tumoral cell lines of the NCI panel in the range 0.47–5.43 μ M. Cytofluorimetric analysis performed on MDA-MB231, a very aggressive breast cancer cell line, which does not express estrogen, progesterone and HER-2/neu receptors, showed that 4 is able to induce prolonged cell cycle arrest at G2/M phase and morphological signs of differentiation. These events are correlated with down-regulation of both cyclin B1 and cdc2, the cyclins involved in G2/M transition, as well as up-regulation of cyclin-dependent kinase (CDK) inhibitor p21 Cip1/Waf1.
- Subjects :
- 0301 basic medicine
Cell cycle checkpoint
Cell Survival
Receptor, ErbB-2
Stereochemistry
Glycoconjugate
Antineoplastic Agents
Antiproliferative activity
Chemistry Techniques, Synthetic
03 medical and health sciences
0302 clinical medicine
Cyclin-dependent kinase
Cell Line, Tumor
Drug Discovery
Humans
Polycyclic Compounds
MDA-MB231
Cyclin B1
Cell Proliferation
Cyclin
Pharmacology
chemistry.chemical_classification
Biological Products
Cyclin-dependent kinase 1
G2/M phase arrest
p21WAF1 inhibitor
biology
Chemistry
Kinase
Drug Discovery3003 Pharmaceutical Science
O-glycoconjugate polycyclic compound
Organic Chemistry
General Medicine
Molecular biology
G2 Phase Cell Cycle Checkpoints
Gene Expression Regulation, Neoplastic
030104 developmental biology
Cell culture
Pyrazolo[3,4-b]pyrazolo[3′,4′:2,3]azepino[4,5-f]azocine
Drug Design
030220 oncology & carcinogenesis
biology.protein
M Phase Cell Cycle Checkpoints
Receptors, Progesterone
Glycoconjugates
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....e8d9b9dcfe974897ca186b2c4bebe3c1