Part I: Synthesis, cancer chemopreventive activity and molecular docking study of novel quinoxaline derivatives

被引：68

作者：

Galal, Shadia A. ^{[1
]}

Abdelsamie, Ahmed S. ^{[1
]}

Tokuda, Harukuni ^{[2
]}

Suzuki, Nobutaka ^{[2
]}

Lida, Akira ^{[3
]}

ElHefnawi, Mahmoud M. ^{[4
]}

Ramadan, Raghda A. ^{[4
]}

Atta, Mona H. E. ^{[4
]}

El Diwani, Hoda I. ^{[1
]}

机构：

[1] Natl Res Ctr, Div Pharmaceut & Drug Ind, Dept Chem Nat & Microbial Prod, Cairo 12622, Egypt

[2] Kanazawa Univ, Grad Sch Med Sci, Clin R&D, Dept Complementary & Alternat Med, Kanazawa, Ishikawa 9208640, Japan

[3] Kinki Univ, Fac Agr, Nara 6318505, Japan

[4] Natl Res Ctr, Ctr Excellence Adv Sci, Biomed Informat & Chemoinformat Grp, Cairo 12622, Egypt

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 01期

关键词：

Synthesis; Quinoxalines; Anti-tumor promoter; Epstein-Barr virus; Two-stage carcinogenesis; 12-O-Tetradecanoylphorbol-13-acetate (TPA); Docking; Protein tyrosine kinase receptor (PTK); BIOLOGICAL EVALUATION; ANTITUMOR AGENT; ETHYL CARBOETHOXYFORMIMIDATE; ACID XK469; INHIBITORS; CELLS; ACTIVATION; COMPLEXES; RECEPTOR; ANALOGS;

D O I：

10.1016/j.ejmech.2010.11.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：327 / 340

页数：14

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