A novel synthetic analog of 5, 8-disubstituted quinazolines blocks mitosis and induces apoptosis of tumor cells by inhibiting microtubule polymerization.

Abstract

Many mitosis inhibitors are powerful anticancer drugs. Tremendous efforts have been made to identify new anti-mitosis compounds for developing more effective and less toxic anti-cancer drugs. We have identified LJK-11, a synthetic analog of 5, 8-disubstituted quinazolines, as a novel mitotic blocker. LJK-11 inhibited growth and induced apoptosis of many different types of tumor cells. It prevented mitotic spindle formation and arrested cells at early phase of mitosis. Detailed in vitro analysis demonstrated that LJK-11 inhibited microtubule polymerization. In addition, LJK-11 had synergistic effect with another microtubule inhibitor colchicine on blocking mitosis, but not with vinblastine or nocodazole. Therefore, LJK-11 represents a novel anti-microtubule structure. Understanding the function and mechanism of LJK-11 will help us to better understand the action of anti-microtubule agents and to design better anti-cancer drugs.

• Authors: Wei Tian, Lili Qin, Qiaoling Song, Li He, Midan Ai, Yi Jin, Zuyu Zhou, Song You, Yaqiu Long, Qiang Yu
• Journal: PloS one (PLoS One) Vol. 5 Issue 5 Pg. e10499 (May 05 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20463925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LJK 11 compound
• Quinazolines
• Tubulin
• Phosphotyrosine
• Colchicine

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colchicine (pharmacology)
• Drug Screening Assays, Antitumor
• Drug Synergism
• G2 Phase (drug effects)
• Humans
• Microtubules (drug effects, metabolism)
• Mitosis (drug effects)
• Phosphorylation (drug effects)
• Phosphotyrosine (metabolism)
• Quinazolines (chemistry, pharmacology)
• Spindle Apparatus (drug effects, metabolism)
• Tubulin (metabolism)