3-substituted 7-phenyl-pyrroloquinolinones show potent cytotoxic activity in human cancer cell lines

被引：43

作者：

Gasparotto, Venusia

Castagliuolo, Ignazio

Ferlin, Maria Grazia

机构：

[1] Univ Padua, Sch Pharm, Dept Pharmaceut Sci, I-35131 Padua, Italy

[2] Univ Padua, Sch Pharm, Dept Histol Microbiol & Med Biotechnol, I-35131 Padua, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 22期

关键词：

D O I：

10.1021/jm070534b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 3-alkyl-substituted 7-phenyl-3H-pyrrolo[3,2-jlquinolin-9-ones (7-PPyQs) was synthesized with the aim to optimize the cytotoxic activity of recently identified PPyQs, promising inhibitors of tubulin polymerization. All compounds inhibited the growth of 11 human tumor cell lines at submicromolar concentrations as well as two human resistant cancer sublines, A549-T12 and A549-T24. FACS analysis indicated that all compounds caused significant arrest of the A549 cell cycle in G(2)/M phase at 0.1 and 1 mu M and a good correlation between the cytotoxicity IC50 and their ability to block the cell cycle was observed.

引用

收藏

页码：5509 / 5513

页数：5

相关论文

共 25 条

[1] Microtubule-targeted anticancer agents and apoptosis [J].

Bhalla, KN .

ONCOGENE, 2003, 22 (56) :9075-9086

[2] The interaction of the B-ring of colchicine with α-tubulin:: A novel footprinting approach [J].

Chaudhuri, AR ;

Seetharamalu, P ;

Schwarz, PM ;

Hausheer, FH ;

Ludueña, RF .

JOURNAL OF MOLECULAR BIOLOGY, 2000, 303 (05) :679-692

[3]

Drukman S, 2002, INT J ONCOL, V21, P621

[4] Synthesis and in vitro and in vivo antitumor activity of 2-phenylpyrroloquinolin-4-ones [J].

Ferlin, MG ;

Chiarelotto, G ;

Gasparotto, V ;

Dalla Via, L ;

Pezzi, V ;

Barzon, L ;

Palù, G ;

Castagliuolo, L .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (09) :3417-3427

[5] Discovering novel chemotherapeutic drugs for the third millennium [J].

Garrett, MD ;

Workman, P .

EUROPEAN JOURNAL OF CANCER, 1999, 35 (14) :2010-2030

[6] Synthesis and biological activity of 7-phenyl-6,9-dihydro-3H-pyrrolo[3,2-f]quinolin-9-ones:: A new class of antimitotic agents devoid of aromatase activity [J].

Gasparotto, V ;

Castagliuolo, I ;

Chiarelotto, G ;

Pezzi, V ;

Montanaro, D ;

Brun, P ;

Palù, G ;

Viola, G ;

Ferlin, MG .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (06) :1910-1915

[7] Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics [J].

Gonçalves, A ;

Braguer, D ;

Kamath, K ;

Martello, L ;

Briand, C ;

Horwitz, S ;

Wilson, L ;

Jordan, MA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (20) :11737-11742

[8]

Hadfield John A, 2003, Prog Cell Cycle Res, V5, P309

[9]

Jordan A, 1998, MED RES REV, V18, P259, DOI 10.1002/(SICI)1098-1128(199807)18:4<259::AID-MED3>3.3.CO

[10]

2-T