Structural simplification of bioactive natural products with multicomponent synthesis.: 2.: Antiproliferative and antitubulin activities of pyrano[3,2-c]pyridones and pyrano[3,2-c]quinolones

被引：163

作者：

Magedov, Igor V. ^{[1
,2
]}

Manpadi, Madhuri ^{[1
]}

Ogasawara, Marcia A. ^{[1
,3
]}

Dhawan, Adriana S. ^{[3
]}

Rogelj, Snezna ^{[3
]}

Van Slambrouck, Severine ^{[1
]}

Steelant, Wim F. A. ^{[1
]}

Evdokimov, Nikolai M. ^{[2
]}

Uglinskii, Pavel Y. ^{[2
]}

Elias, Eerik M. ^{[1
]}

Knee, Erica J. ^{[1
]}

Tongwa, Paul ^{[4
]}

Antipin, Mikhail Yu. ^{[4
,5
]}

Kornienko, Alexander ^{[1
]}

机构：

[1] New Mexico Inst Min & Technol, Dept Chem, Socorro, NM 87801 USA

[2] KA Timiryazev Agr Acad, Dept Organ Chem, Moscow 127550, Russia

[3] New Mexico Inst Min & Technol, Dept Biol, Socorro, NM 87801 USA

[4] New Mexico Highlands Univ, Dept Nat Sci, Las Vegas, NM 87701 USA

[5] Russian Acad Sci, Inst Organoelement Cpds, Moscow, Russia

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 08期

关键词：

D O I：

10.1021/jm701499n

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyrano[3,2-c]pyridone and pyrano[3,2-c]quinolone structural motifs are commonly found in alkaloids manifesting diverse biological activities. As part of a program aimed at structural simplification of bioactive natural products utilizing multicomponent synthetic processes, we developed compound libraries based on these privileged heterocyclic scaffolds. The selected library members display low nanomolar antiproliferative activity and induce apoptosis in human cancer cell lines. Mechanistic studies reveal that these compounds induce cell cycle arrest in the G2/M phase and block in vitro tubulin polymerization. Because of the successful clinical use of microtubule-targeting agents, these heterocyclic libraries are expected to provide promising new leads in anticancer drug design.

引用

页码：2561 / 2570

页数：10

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