Synthesis and antiproliferative activity of indolizine derivatives incorporating a cyclopropylcarbonyl group against Hep-G2 cancer cell line.

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Shen YM, Lv PC, Chen W, Liu PG, Zhang MZ, Zhu HL

Synthesis and antiproliferative activity of indolizine derivatives incorporating a cyclopropylcarbonyl group against Hep-G2 cancer cell line.

Eur J Med Chem. 2010 Jul;45(7):3184-90. doi: 10.1016/j.ejmech.2010.02.056. Epub 2010 Mar 1.

PubMed ID

20304535 [ View in PubMed

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Abstract

Indolizine and annulated indolizine derivatives incorporating a cyclopropylcarbonyl group were synthesized in a one pot procedure by the tanden reactions of [3+2] cycloaddition of the corresponding N-ylide with electron deficient alkene. Seventeen indolizine derivatives were reported for the first time. All the compounds were examined for their antiproliferative activity against the human hepatocellular liver carcinoma (Hep-G2) cell line by MTT method. Among the compounds tested, 5a, 5d, 5 g and 5 j showed the most favorable activities with IC(50) values of 0.39, 0.48, 0.29 and 0.20 microg/mL. Especially, compound 5 j displayed potent antiproliferative activities with IC(50) value of 0.20 microg/mL, and showed significant EGFR kinase inhibitory activity with IC(50) value of 0.085 microM. Docking simulations of 5 j were carried out to illustrate the binding mode of the molecular into the EGFR active site.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Gefitinib	Epidermal growth factor receptor	IC 50 (nM)	33	N/A	N/A	Details