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新型喹喔啉-2(1H)-酮作为具有酪氨酸激酶受体抑制作用的抗肿瘤活性剂的设计、合成及分子对接研究,并研究其环氧合酶-2活性。

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.

作者信息

Galal Shadia A, Khairat Sarah H M, Ragab Fatma A F, Abdelsamie Ahmed S, Ali Mamdouh M, Soliman Salwa M, Mortier Jérémie, Wolber Gerhard, El Diwani Hoda I

机构信息

Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622, Cairo, Egypt.

Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622, Cairo, Egypt.

出版信息

Eur J Med Chem. 2014 Oct 30;86:122-32. doi: 10.1016/j.ejmech.2014.08.048. Epub 2014 Aug 15.

Abstract

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.

摘要

在继续我们的工作中,合成了新的喹喔啉 - 2(1H)-酮,以研究它们对HepG - 2和MCF - 7的细胞毒性作用及其对人酪氨酸激酶(TRK)的影响。发现化合物12、18、15、13、11a、20和16分别比顺铂对HepG2更具活性且对TRK具有选择性。此外,与顺铂相比,化合物12、18、20、13、14和22分别对MCF - 7表现出明显的活性且对人TRK具有选择性。还进行了分子对接研究,以全面了解可能的结合模式并总结合成化合物的构效关系。此外,还研究了抗炎活性。发现化合物12、15、18和22对COX - 2具有强效和选择性。

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