Parallel solid synthesis of inhibitors of the essential cell division FtsZ enzyme as a new potential class of antibacterials

被引：32

作者：

Paradis-Bleau, Catherine

Beaumont, Melanie

Sanschagrin, Francois

Voyer, Normand

Levesque, Roger C. ^{[1
]}

机构：

[1] Univ Laval, Fac Med, Dept Med Biol, CREFSIP, Ste Foy, PQ G1K 7P4, Canada

[2] Univ Laval, Fac Sci & Genie, Dept Chim, CREFSIP, Ste Foy, PQ G1K 7P4, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 03期

关键词：

parallel synthesis; GTP analogues; Pseudomonas aeruginosa; FtsZ inhibitors; Staphylococcus aureus;

D O I：

10.1016/j.bmc.2006.11.015

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：

As a model system for designing new inhibitors of bacterial cell division, we studied the essential and highly conserved FtsZ GTPase from Pseudomonas aeruginosa. A collection of GTP analogues were prepared using the solid-phase parallel synthesis approach. The synthesized GTP analogues inhibited the GTPase activity of FtsZ with IC50 values between 450 mu M and 2.6 mM, and 5 compounds inhibited Staphylococcus aureus growth in a biological assay. The FtsZ spectrophotometric assay developed for screening of synthesized compounds is the first step in identification of antibacterials targeting the bacterial cell division essential proteins. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1330 / 1340

页数：11

共 51 条

[1] CONVERSION OF SERINE TO STEREOCHEMICALLY PURE BETA-SUBSTITUTED ALPHA-AMINO-ACIDS VIA BETA-LACTONES [J].