title: Part I: Synthesis, cancer chemopreventive activity and molecular docking study of novel quinoxaline derivatives.
abstract: The reaction of o-phenylene diamine and ethyl oxamate is reinvestigated and led to 3-aminoquinoxalin-2(1H)-one rather than benzimidazole-2-carboxamide as was previously reported. The structure of the obtained quinoxaline has been confirmed by X-ray. The anti-tumor activity of synthesized quinoxalines 1-21 has been evaluated by studying their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds 1-21, compounds 12, 8, 13, 18, 17 and 19, respectively, demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity and their effects being stronger than that of a representative control, oleanolic acid. Furthermore, compound 12 exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. The result of the present investigation indicated that compound 12 might be valuable as a potent cancer chemopreventive agent. Moreover, the molecular docking into PTK (PDB: 1t46) has been done for lead optimization of the aforementioned compounds as potential PTK inhibitors.
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki 12622, Cairo, Egypt. 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: 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: Mahmoud M
authors.initials: MM
authors.lastname: Elhefnawi
authors.forename: Raghda A
authors.initials: RA
authors.lastname: Ramadan
authors.forename: Mona H E
authors.initials: MH
authors.lastname: Atta
authors.forename: Hoda I
authors.initials: HI
authors.lastname: El Diwani
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D005260:Female; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000517:prevention & control* / Q000821:virology; D011487:Protein Conformation; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000378:metabolism; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D015203:Reproducibility of Results
chemical_list: D000956:Antigens, Viral; D000970:Antineoplastic Agents; C033305:Epstein-Barr virus early antigen; D011810:Quinoxalines; D019009:Proto-Oncogene Proteins c-kit