Synthesis of a new 4-aza-2,3-didehydropodophyllotoxin analogues as potent cytotoxic and antimitotic agents

被引：61

作者：

Kamal, Ahmed ^{[1
]}

Suresh, Paidakula ^{[1
]}

Mallareddy, Adla ^{[1
]}

Kumar, Banala Ashwini ^{[1
]}

Reddy, Papagari Venkat ^{[1
]}

Raju, Paidakula ^{[1
]}

Tamboli, Jaki R. ^{[1
]}

Shaik, Thokhir B. ^{[2
]}

Jain, Nishant ^{[2
]}

Kalivendi, Shasi V. ^{[2
]}

机构：

[1] Indian Inst Chem Technol, Div Organ Chem, Hyderabad 500607, Andhra Pradesh, India

[2] Indian Inst Chem Technol, Ctr Chem Biol, Hyderabad 500607, Andhra Pradesh, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 07期

关键词：

Multicomponent synthesis; Podophyllotoxin; Anticancer activity; Tubulin polymerization activity; G2/M Cell cycle arrest; Immunohistochemistry; Caspase-3; activation; BIOLOGICAL EVALUATION; MULTICOMPONENT REACTIONS; PODOPHYLLOTOXIN; DISCOVERY; FACILE; DERIVATIVES; CONGENERS; NPF;

D O I：

10.1016/j.bmc.2011.02.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of novel conjugates of 4-aza-2,3-didehydropodophyllotoxins (11a-w) were synthesized by a straightforward one-step multicomponent synthesis that demonstrated cytotoxicity against five human cancer cell lines (breast, oral, colon, lung and ovarian). All the twenty three compounds (11a-w) have been examined for the inhibition of tubulin polymerization. Among these compounds, 11a, 11k and 11p exhibited inhibition of polymerization tubulin comparable to podophyllotoxin apart from disruption of microtubule organization within the cells. Flow cytometric analysis showed that these compounds (11a, 11k and 11p) arrested the cell cycle in the G2/M phase of cell cycle leading to caspase-3 dependent apoptotic cell death. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2349 / 2358

页数：10

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