Synthesis, EGFR-TK inhibition and anticancer activity of new quinoxaline derivatives

被引：29
作者：
Ahmed, Eman A. [1 ]
Mohamed, Mamdouh F. A. [2 ]
Omran, Ahmed [3 ]
Salah, Hanan [1 ]
机构：
[1] Sohag Univ, Fac Sci, Dept Chem, Sohag 82524, Egypt
[2] Sohag Univ, Fac Pharm, Dept Pharmaceut Chem, Sohag, Egypt
[3] Menia Univ, Fac Pharm, Dept Pharmacol, Al Minya, Egypt
来源：
SYNTHETIC COMMUNICATIONS | 2020年 / 50卷 / 19期
关键词：
Anti-proliferative activity; heterocyclization; molecular docking; nucleophilic reactions; quinoxaline derivatives; X-ray crystallography; ONE-POT; ANTIMICROBIAL ACTIVITY; BIOLOGICAL EVALUATION; CORROSION-INHIBITORS; EFFICIENT PROTOCOL; IN-VITRO; DESIGN; OXIDATION; CATALYST; SEARCH;
D O I：
10.1080/00397911.2020.1787448
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Ethyl 4-substituted-3-oxo-quinoxaline-2-carboxylates3-5were obtainedviaalkylation of ethyl 3-oxo-3,4-dihydroquinoxaline-2-carboxylate (1). Compound1was heterocyclized using hydrazines, ethylenediamine, and ethanolamine to give pyrazoloquinoxalines6, 7, diazepinoquinoxaline8, and oxazepinoquinoxaline10. The quinoxaline-2-carboxamides9, 11, 12were preparedviacondensation of compound1with different amines. Compound1was thiated using Lawesson's reagent affording quinoxaline-3-thione13, in fair yield. In addition, the reaction of 4-methyl-3-oxoquinoxaline3with some binucleophiles led to a series of new oxoquinoxaline derivatives14-18. The molecular structure of compounds1, 3,and9was confirmed by X-ray crystallography. The anti-proliferative activity showed that among all the tested compounds, compounds3, (IC(50)2.51 +/- 3.0, 4.22 +/- 1.6 and 2.27 +/- 1.9 mu M),11(IC(50)1.32 +/- 2.61, 1.41 +/- 1.23 and 1.18 +/- 1.91 mu M) and17(IC(50)1.72 +/- 1.32, 1.85 +/- 0.94 and 1.92 +/- 4.83 mu M) showed noteworthy anti-proliferative effects against the three cancer cell lines, HCT116, HePG2 and MCF7, respectively, compared to the reference drugs doxorubicin (IC(50)1.41 +/- 0.58, 0.90 +/- 0.62 and 1.01 +/- 3.02 mu M) and erlotinib (IC(50)1.63 +/- 0.81, 1.57 +/- 0.62 and 1.49 +/- 0.54 mu M). Compounds3 (0.899 nM),11(0.508 nM) and17(0.807) showed strong EGFR inhibitory activity compared to Erlotinib (0.439 nM) and these results are in agreement with the docking study. These results suggest that compounds could probably be promising anticancer agents with EGFR inhibitory activity.
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页码：2924 / 2940
页数：17
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