Synthesis and Biological evaluation of novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxins as anticancer compounds

被引：21

作者：

Hyder, Irfan ^{[1
,4
]}

Yedlapudi, Deepthi ^{[2
]}

Kalivendi, Shasi V. ^{[2
]}

Khazir, Jabeena ^{[3
]}

Ismail, Tabasum ^{[3
]}

Nalla, Naresh ^{[1
]}

Miryala, Sreekanth ^{[1
,4
]}

Kumar, Halmuthur M. Sampath ^{[1
,4
]}

机构：

[1] CSIR Indian Inst Chem Technol, NPC Div, Hyderabad 500007, Andhra Pradesh, India

[2] CSIR Indian Inst Chem Technol, Ctr Chem Biol Div, Hyderabad 500007, Andhra Pradesh, India

[3] Indian Inst Integrat Med, Div Med Chem, Jammu 180001, India

[4] CSIR Indian Inst Chem Technol, Acad Sci & Innovat Res, Hyderabad 500007, Andhra Pradesh, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 14期

关键词：

Tetrazolyl podophyllotoxin; Anticancer activity; Tubulin polymerization; DNA TOPOISOMERASE-II; HUISGEN 1,3-DIPOLAR CYCLOADDITION; CLICK CHEMISTRY APPROACH; INSECTICIDAL ACTIVITY; ANTITUMOR AGENTS; ONE-POT; DERIVATIVES; TETRAZOLES; INHIBITORS; APOPTOSIS;

D O I：

10.1016/j.bmcl.2015.04.053

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 4 beta-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxin derivatives were synthesized by employing azide-nitrile click chemistry approach. All the derivatives were evaluated for their cytotoxicity against a panel of four human cancer cell lines and their IC50 values were found to be in the range of 2.4-29.06 mu M. The cytotoxicity exhibited by the majority of test compounds were found to comparable and often more effective than doxorubicin and all compounds exhibited higher cytotoxicity on A-549 cell lines. Cell cycle analysis showed that the novel 4 beta-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxins resulted in cell cycle arrest at G2/M phase and were also found to be the potent inhibitors of tubulin polymerization in vitro. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：2860 / 2863

页数：4

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