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对接研究、一些新型嗪取代 9-苯胺吖啶衍生物的合成、表征及其作为拓扑异构酶 II 抑制剂的抗氧化和抗癌活性评价。

Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and anticancer activities as topoisomerase II inhibitors.

机构信息

Department of Pharmaceutical Chemistry, JSS College of Pharmacy, (Off Campus, JSS University, Mysore), Udhagamandalam 643001, Tamilnadu, India.

出版信息

Eur J Med Chem. 2012 Oct;56:217-24. doi: 10.1016/j.ejmech.2012.08.025. Epub 2012 Aug 31.

Abstract

A series of 9-anilinoacridines substituted with oxazine derivatives were synthesized to evaluate their antioxidant and anticancer activity against Daltons Lymphoma Ascites (DLA) cell growth by in vitro method. It was revealed that these conjugates exhibited significant antioxidant and anticancer activity (inhibition of DLA cell proliferation). Among these agents, compounds 5a, 5h, 5i, 5j were the most cytotoxic with CTC(50) value of 140-250 μg/mL. The docking studies of the synthesized compounds were performed towards the key Topoisomerase II (1QZR) by using Schrodinger Maestro 9.2 version. The oxazine substituted 9-anilinoacridine derivatives 5a, 5h, 5i, 5j have significant anticancer activity as topoisomerase II inhibitors.

摘要

一系列带有嗪衍生物的 9-苯胺吖啶被合成,以通过体外方法评估它们对达尔顿淋巴瘤腹水(DLA)细胞生长的抗氧化和抗癌活性。结果表明,这些化合物具有显著的抗氧化和抗癌活性(抑制 DLA 细胞增殖)。在这些化合物中,化合物 5a、5h、5i、5j 的细胞毒性最强,CTC(50) 值为 140-250μg/mL。通过使用 Schrodinger Maestro 9.2 版本,对合成的化合物进行了针对关键拓扑异构酶 II(1QZR)的对接研究。带有嗪取代基的 9-苯胺吖啶衍生物 5a、5h、5i、5j 具有作为拓扑异构酶 II 抑制剂的显著抗癌活性。

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