Synthesis and antiproliferative activity of a natural like glycoconjugate polycyclic compound

• 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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