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

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.

• Authors: Yong-Miao Shen, Peng-Cheng Lv, Wu Chen, Peng-Gang Liu, Ming-Zhu Zhang, Hai-Liang Zhu
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 45 Issue 7 Pg. 3184-90 (Jul 2010) ISSN: 1768-3254 [Electronic] France
• PMID: 20304535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Indolizines
• indolizine
• ErbB Receptors

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, metabolism, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• ErbB Receptors (chemistry, metabolism)
• Humans
• Indolizines (chemical synthesis, chemistry, metabolism, pharmacology)
• Inhibitory Concentration 50
• Models, Molecular
• Molecular Conformation