Synthesis and biological evaluation of fluoro analogues of antimitotic phenstatin

被引：32

作者：

Ghinet, Alina ^{[1
,2
,3
]}

Tourteau, Aurelien ^{[2
,4
]}

Rigo, Benoit ^{[2
,3
]}

Stocker, Vivien ^{[2
,3
]}

Leman, Marie ^{[2
,3
]}

Farce, Amaury ^{[2
,4
]}

Dubois, Joelle ^{[5
]}

Gautret, Philippe ^{[2
,3
]}

机构：

[1] Alexandru Ioan Cuza Univ, Fac Chem, Dept Organ Chem, Iasi 700506, Romania

[2] Univ Lille Nord de France, F-59000 Lille, France

[3] UCLille, EA GRIIOT 4481, Lab Pharmacochim, HEI, F-59046 Lille, France

[4] Inst Chim Pharmaceut Albert Lespagnol, EA GRIIOT 4481, IFR114, F-59006 Lille, France

[5] CNRS, Inst Chim Subst Nat, UPR2301, Ctr Rech Gif, F-91198 Gif Sur Yvette, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 11期

关键词：

Phenstatin; Tubulin; Antimitotic agent; Fluorobenzophenone; Eaton's reagent; ANTINEOPLASTIC AGENTS; TUBULIN POLYMERIZATION; ANTICANCER ACTIVITY; COMBRETASTATIN A4; BINDING; ISOCOMBRETASTATINS; DERIVATIVES; INHIBITION; COLCHICINE; CHEMISTRY;

D O I：

10.1016/j.bmc.2013.03.064

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：

With the aim of investigating the influence of fluorine, in particular on the A-ring, a new series of fluoro analogues (7a-l) of phenstatin (3) was synthesized and tested for interactions with tubulin polymerization and evaluated for cytotoxicity on an NCI-60 human cancer cell lines panel. We have shown that the replacement of 3,4,5-trimethoxyphenyl A-ring of phenstatin with 2,4,5-trifluoro-3-methoxyphenyl unit, results in the conservation of both antitubulin and cytotoxic effect. Fluoro isocombretastatin 7k was the most effective anticancer agent in the present study and demonstrated the highest antiproliferative potential on leukemia cell lines SR (GI(50) = 15 nM) and HL-60(TB) (GI(50) = 23 nM) and on melanoma cell line MDA-MB-435 (GI(50) = 19 nM). (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：2932 / 2940

页数：9

共 53 条

[1] Synthesis and anticancer activity of analogues of phenstatin, with a phenothiazine A-ring, as a new class of microtubule-targeting agents [J].