Design, synthesis and biological evaluation of 4′-demethyl-4-deoxypodophyllotoxin derivatives as novel tubulin and histone deacetylase dual inhibitors

被引：13

作者：

Zhang, Xuan ^{[1
]}

Zhang, Jie ^{[2
]}

Su, Mingbo ^{[3
]}

Zhou, Yubo ^{[3
]}

Chen, Yi ^{[2
]}

Li, Jia ^{[3
]}

Lu, Wei ^{[1
]}

机构：

[1] E China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Inst Drug Discovery & Dev, Shanghai 200062, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China

来源：

RSC ADVANCES | 2014年 / 4卷 / 76期

基金：

中国国家自然科学基金;

关键词：

GROWTH-FACTOR RECEPTOR; T-CELL LYMPHOMA; ANTITUMOR-ACTIVITY; TOPOISOMERASE-II; IN-VIVO; POTENT INHIBITORS; CANCER-THERAPY; DISCOVERY; APOPTOSIS; AGENTS;

D O I：

10.1039/c4ra05508j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A new class of 4'-demethyl-4-deoxypodophyllotoxin derivatives has been designed and synthesized as tubulin-HDAC dual inhibitors. Biological evaluation of these hybrids included the inhibitory activity of HDAC, in vitro cell cycle analysis in HCT-116 cells as well as cytotoxicity against two cancer cell lines (A549 and HCT116). The distance and angle between the HDAC capping group and the zinc binding group were systematically varied. Compounds 14a and 14c showed most potent dual inhibitory activity and powerful antiproliferative activity on HCT116 and A549 cell lines.

引用

页码：40444 / 40448

页数：5

共 44 条

[1] It's about time: Scheduling alters effect of histone deacetylase inhibitors on camptothecin-treated cells [J].