Synthesis and evaluation of novel podophyllotoxin analogs

被引：13

作者：

Li, Jie ^{[1
,2
,3
]}

Hua, Hui Ming ^{[3
]}

Tang, Yan Bo ^{[1
,2
]}

Zhang, Shipeng ^{[1
,2
]}

Ohkoshi, Emika ^{[4
]}

Lee, Kuo-Hsiung ^{[4
,5
]}

Xiao, Zhi Yan ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Act Subst Discovery & Druggabil E, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Design & Discovery, Shenyang 110016, Peoples R China

[4] Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA

[5] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 13期

关键词：

Podophyllotoxin; Structural modification; Cytotoxicity; ANTITUMOR AGENTS; DERIVATIVES;

D O I：

10.1016/j.bmcl.2012.05.033

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Because prior studies have shown inconsistency between structure-activity relationships for podophyllotoxin derivatives as topoisomerase II inhibitors and cytotoxic agents, eight novel podophyllotoxin analogs were synthesized to further explore the effects of structural variations on both A and D rings on activity. The new compounds contain a 4,5-dimethoxy substituted A ring and opened D-ring variants and were prepared by appropriate functional and stereochemical operations at the methylenedioxy group, C7, C8, and C80. Four compounds (15, 18, 21 and 22) demonstrated noticeable inhibitory activity against A549, DU145, KB and KBvin tumor cells, and the most active compound 18 showed IC50 values less than 10 mu g/mL. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4293 / 4295

页数：3

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