Design, synthesis and molecular docking study of novel quinoxalin-2(1H)-ones as anti-tumor active agents with inhibition of tyrosine kinase receptor and studying their cyclooxygenase-2 activity

被引：125
作者：
Galal, Shadia A. [1 ]
Khairat, Sarah H. M. [1 ]
Ragab, Fatma A. F. [2 ]
Abdelsamie, Ahmed S. [1 ]
Ali, Mamdouh M. [3 ]
Soliman, Salwa M. [4 ]
Mortier, Jeremie [4 ]
Wolber, Gerhard [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] Cairo Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo, Egypt
[3] Natl Res Ctr, Div Genet Engn & Biotechnol, Dept Biochem, Cairo 12622, Egypt
[4] Free Univ Berlin, Inst Pharm, Dept Pharmaceut Chem, D-14195 Berlin, Germany
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 86卷
关键词：
Synthesis; Quinoxalines; Antitumor activity; Cyclooxygenase-2; Docking; Protein tyrosine kinase; CANINE COX-2 INHIBITORS; BIOLOGICAL EVALUATION; PART; ANTICANCER; PYRAZOLE; DERIVATIVES; XK469; DISCOVERY; POTENT;
D O I：
10.1016/j.ejmech.2014.08.048
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
On continuation to our work, new quinoxalin-2(1H)-ones were synthesized to study their cytotoxic effect against HepG-2 and MCF-7 with their effect on the human tyrosine kinase (TRK). Compounds 12, 18, 15, 13,11a, 20 and 16, respectively, were found to be more potent than cisplatin against HepG2 and selective to TRK. Also, compounds 12, 18, 20, 13, 14, and 22, respectively, exhibited decidedly activity against MCF-7 and selectivity against human TRK compared to cisplatin. A molecular docking study was also performed to gain comprehensive understanding into plausible binding modes and to conclude the structure activity relationships of the synthesized compounds. Moreover, anti-inflammatory activity was studied. Compounds 12, 15, 18 and 22 were found to be potent and selective against COX-2. (C) 2014 Elsevier Masson SAS. All rights reserved.
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收藏
页码：122 / 132
页数：11
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