New farnesyltransferase inhibitors in the phenothiazine series

被引：39

作者：

Belei, Dalila ^{[1
]}

Dumea, Carmen ^{[1
]}

Samson, Alexandrina ^{[1
]}

Farce, Amaury ^{[2
,3
]}

Dubois, Joelle ^{[4
]}

Bicu, Elena ^{[1
]}

Ghinet, Alina ^{[1
,2
,5
]}

机构：

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

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

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

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 14期

关键词：

Farnesyltransferase inhibitor; Anticancer agent; Phenothiazine; Triazole; FARNESYL TRANSFERASE INHIBITORS; PROTEIN FARNESYLTRANSFERASE; RAS GENES; N-RAS; CANCER; ASSAY; CARCINOMAS; BMS-214662; PANCREAS; AGENTS;

D O I：

10.1016/j.bmcl.2012.06.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The biological screening of the chemical library of our Organic Chemistry Department, carried out on an automated fluorescence-based FTase assay, allowed us to discover that a phenothiazine derivative (1d) was an inhibitor of farnesyltransferase. Three new series of human farnesyltransferase inhibitors, based on a phenothiazine scaffold, were synthesized with protein farnesyltransferase inhibition potencies in the low micromolar range. Ester derivative 9d was the most active compound in these series. Four synthesized compounds were evaluated for their antiproliferative activity on a NCI-60 cancer cell line panel. The modest results obtained in this preliminary investigation showed that mixing the phenothiazine and the 1,2,3-triazole motif in the structure of a single compound can lead to new scaffolds in the field of farnesyltransferase inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4517 / 4522

页数：6

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