Design, synthesis and biological evaluation of novel glycosylated diphyllin derivatives as topoisomerase II inhibitors

被引:26
|
作者
Shi, Da-Kuo [2 ]
Zhang, Wei [1 ]
Ding, Ning [1 ]
Li, Ming [2 ]
Li, Ying-Xia [1 ]
机构
[1] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
[2] Ocean Univ China, Sch Med & Pharm, Qingdao 266003, Peoples R China
关键词
Diphyllin; Topo II inhibitors; Synthesis; Anticancer; Structure-activity relationship; JUSTICIA-PROCUMBENS; ARYLNAPHTHALENE LIGNANS; CYTOTOXICITY; APOPTOSIS; GLYCOSIDES; SALVICINE; ANALOGS; AGENTS; ASSAY;
D O I
10.1016/j.ejmech.2011.11.011
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Recently, a novel glycosylated diphyllin derivative 11 which exhibiting potent anticancer activity by targeting topoisomerase II alpha was reported by our group. In order to provide more molecules for structure-activity relationship (SAR) studies, 12 new glycosylated diphyllin analogs have been designed, synthesized, and evaluated for their biological activities. The SAR analysis revealed that (i) the sugar moiety on the diphyllin is essential for the anticancer activity; (ii) equatorial C4 '-OH on the sugar is superior to the axial one, and (iii) a proper cyclic lipophilic group at the C4' and C6' of sugar might enhance the anticancer activity. (C) 2011 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:424 / 431
页数:8
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