title: Design, synthesis and structure-activity relationship of novel quinoxaline derivatives as cancer chemopreventive agent by inhibition of tyrosine kinase receptor.
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.
authors.affiliation: 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.
authors.forename: Shadia A
authors.initials: SA
authors.lastname: Galal
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Abdelsamie
authors.forename: Salwa M
authors.initials: SM
authors.lastname: Soliman
authors.forename: Jeremie
authors.initials: J
authors.lastname: Mortier
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
authors.forename: Mamdouh M
authors.initials: MM
authors.lastname: Ali
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Lida
authors.forename: Raghda A
authors.initials: RA
authors.lastname: Ramadan
authors.forename: Hoda I
authors.initials: HI
authors.lastname: El Diwani
mesh_terms: D000956:Antigens, Viral / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000956:Antigens, Viral; D000970:Antineoplastic Agents; C033305:Epstein-Barr virus early antigen; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; D020794:Receptor Protein-Tyrosine Kinases
keywords: Cancer chemopreventive activity; Docking; Epstein–Barr virus; Protein tyrosine kinase; Quinoxalines; Synthesis