Design, synthesis and structure-activity relationship of novel quinoxaline derivatives as cancer chemopreventive agent by inhibition of tyrosine kinase receptor

Shadia A Galal; Ahmed S Abdelsamie; Salwa M Soliman; Jeremie Mortier; Gerhard Wolber; Mamdouh M Ali; Harukuni Tokuda; Nobutaka Suzuki; Akira Lida; Raghda A Ramadan; Hoda I El Diwani

doi:10.1016/j.ejmech.2013.07.049

Design, synthesis and structure-activity relationship of novel quinoxaline derivatives as cancer chemopreventive agent by inhibition of tyrosine kinase receptor

Eur J Med Chem. 2013 Nov:69:115-24. doi: 10.1016/j.ejmech.2013.07.049. Epub 2013 Aug 13.

Authors

Shadia A Galal¹, Ahmed S Abdelsamie, Salwa M Soliman, Jeremie Mortier, Gerhard Wolber, Mamdouh M Ali, Harukuni Tokuda, Nobutaka Suzuki, Akira Lida, Raghda A Ramadan, Hoda I El Diwani

Affiliation

¹ Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Center, Dokki, 12622 Cairo, Egypt. Electronic address: sh12galal@yahoo.com.

PMID: 24013411
DOI: 10.1016/j.ejmech.2013.07.049

Abstract

The cancer chemopreventive activity of quinoxaline derivatives 1-20 has been evaluated by studying the inhibitory effect on Epstein-Barr virus early antigen (EBV-EA) activation. The quinoxaline derivatives 1-20 showed inhibitory effect on EBV-EA activation without cytotoxicity on Raji cells. All compounds exhibited dose dependent inhibitory activities, most of them showed significant activity at 1000 mol ratio/12-O-tetradecanoylphorbol-13-acetate (TPA). Compounds 7 and 9 exhibited stronger inhibitory effects on the EBV-EA activation than that of the representative control, oleanolic acid, at the highest measured concentration. In addition, compounds 7-10 showed potent and selective inhibition of human tyrosine kinase (TRK) in liver cancer HepG2 and breast cancer MCF-7 cell lines similar to the positive control, doxorubicin.

Keywords: Cancer chemopreventive activity; Docking; Epstein–Barr virus; Protein tyrosine kinase; Quinoxalines; Synthesis.

MeSH terms

Antigens, Viral / metabolism*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Design*
Hep G2 Cells
Humans
MCF-7 Cells
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Quinoxalines / chemical synthesis
Quinoxalines / chemistry
Quinoxalines / pharmacology*
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
Receptor Protein-Tyrosine Kinases / metabolism
Structure-Activity Relationship

Substances

Antigens, Viral
Antineoplastic Agents
Epstein-Barr virus early antigen
Protein Kinase Inhibitors
Quinoxalines
Receptor Protein-Tyrosine Kinases