| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1394920 | European Journal of Medicinal Chemistry | 2016 | 10 Pages |
•A natural like O-glycoconjugate polycyclic compound 4 was synthesized.•Derivative 4 was evaluated by NCI for its in vitro antiproliferative activity.•It caused 50% growth inhibition in the range 0.47–5.43 μM.•Compound 4 treatment induced a prolonged arrest of MDA-MB-231 cells at G2/M phase.•This is due to cyclin B1 and cdc2 down-regulation and p21 expression up-regulation.
A natural like O-glycoconjugate polycyclic compound 4 was obtained by a multistep procedure starting from N-(3-methyl-1-(4-nitrophenyl)-1H-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 μM. 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.
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