N-Phenyl-N′-(2-chloroethyl)urea analogues of combretastatin A-4:: Is the N-phenyl-N′-(2-chloroethyl)urea pharmacophore mimicking the trimethoxy phenyl moiety?

被引：30

作者：

Fortin, Sebastien

Moreau, Emmanuel ^{[1
]}

Lacroix, Jacques

Teulade, Jean-Claude

Patenaude, Alexandre

C-Gaudreault, Rene

机构：

[1] Univ Laval, Hop St Francois Assise, CHUQ, Ctr Rech,Unite Biotechnol & Bioingn, Laval, PQ G1L 3L5, Canada

[2] Univ Clermont 1, UFR Pharm, Lab Chim Organ, F-63001 Clermont Ferrand, France

[3] INSERM, U484, F-63001 Clermont Ferrand, France

[4] Ctr Jean Perrin, F-63001 Clermont Ferrand, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 07期

关键词：

D O I：

10.1016/j.bmcl.2007.01.023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel N-phe.rlyl-N'-(2-chloroethyl)urea derivatives potentially mimicking the structure of combretastatin A-4 were synthesized and tested for their cell growth inhibition and their binding to the colchicine-binding site of beta-tubulin. Compounds 2a, 3a, and 3b were found to inhibit cell growth at the micromolar level on four human tumor cell lines. Flow cytometric analysis indicates that the new compounds act as antimitotics and arrest the cell cycle in G(2)/M phase. Covalent binding of 2a, 3a, and 3b to the colchicine-binding site of beta-tubulin was confirmed also using SDS-PAGE and competition assays. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2000 / 2004

页数：5

共 50 条

[1] ANTINEOPLASTIC AGENTS .15. INTRAMOLECULAR REACTIONS OF N-PHENYL-N'-BIS(2-CHLOROETHYL)UREA
PETTIT, GR
BLONDA, DS
UPHAM, RA
CANADIAN JOURNAL OF CHEMISTRY, 1965, 43 (06): : 1798 - &
[2] PHENYL N'-(2-CHLOROETHYL)AZIRIDINEPHOSPHORAMIDATE
ROTH, HJ
LENIG, A
ARCHIV DER PHARMAZIE, 1984, 317 (08) : 733 - 734
[3] Synthesis, antiproliferative activity evaluation and structure-activity relationships of novel aromatic urea and amide analogues of N-phenyl-N′-(2-chloroethyl)ureas
Fortin, Sebastien
Moreau, Emmanuel
Lacroix, Jacques
Cote, Marie-France
Petitclerc, Eric
C-Gaudreault, Rene
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2010, 45 (07) : 2928 - 2937
[4] Mechanism of action of N-phenyl-N′-(2-chloroethyl)ureas in the colchicine-binding site at the interface between α-and β-tubulin
Fortin, Sebastien
Wei, Lianhu
Moreau, Emmanuel
Labrie, Philippe
Petitclerc, Eric
Kotra, Lakshmi P.
Gaudreault, Rene C.
BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (10) : 3690 - 3697
[5] Tubulin-binding antimitotic agents:: Synthesis and structure activity-relationship study of N-phenyl-N′-(2-chloroethyl)urea series mimicking colchicinoids on microtubule assembly
Fortin, Sebastien
Moreau, Emmanuel
Desjardins, Michel
Rousseau, Jean L. C.
Lacroix, Jacques
C-Gaudreault, Rene
Kotra, Lakshmi P.
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 231
[6] Characterization of the Covalent Binding of N-Phenyl-N′-(2-chloroethyl)ureas to β-Tubulin: Importance of Glu198 in Microtubule Stability
Fortin, Sebastien
Bouchon, Bernadette
Chambon, Christophe
Lacroix, Jacques
Moreau, Emmanuel
Chezal, Jean-Michel
Degoul, Francoise
C-Gaudreault, Rene
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2011, 336 (02): : 460 - 467
[7] TOSYLATION OF N-PHENYL-N'-(3-HYDROXYPROPYL) UREA
FERRIS, AF
SALERNI, OL
SCHUTZ, BA
JOURNAL OF PHARMACEUTICAL SCIENCES, 1966, 55 (02) : 209 - &
[8] CYTOKININ ACTIVITY OF N-PHENYL-N'-(4-PYRIDYL)UREA DERIVATIVES
TAKAHASHI, S
SHUDO, K
OKAMOTO, T
YAMADA, K
ISOGAI, Y
PHYTOCHEMISTRY, 1978, 17 (08) : 1201 - 1207
[9] ISOMERIZATION CYCLIZATION OF N-PHENYL-N'-(ORTHO-CYANOPHENYL)-UREA
BARASHKOV, NN
ZIMINA, LA
TELESHOV, EN
PRAVEDNIKOV, AN
DOKLADY AKADEMII NAUK SSSR, 1978, 240 (04): : 847 - 850
[10] N-phenyl-N′-(2-chloroethyl)ureas (CEU) as potential antineoplastic agents.: Part 2:: Role of ω-hydroxyl group in the covalent binding to β-tubulin
Fortin, Sebastien
Moreau, Emmanuel
Patenaude, Alexandre
Desjardins, Michel
Lacroix, Jacques
Rousseau, Jean L. C.
C-Gaudreault, Ren
BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (03) : 1430 - 1438

← 1 2 3 4 5 →