Discovery of potent inhibitors of pseudomonal quorum sensing via pharmacophore modeling and in silico screening

被引：54

作者：

Taha, Mutasem O. ^{[1
]}

Al-Bakri, Amal G. ^{[1
]}

Zalloum, Waleed A. ^{[1
]}

机构：

[1] Univ Jordan, Fac Pharm, Amman, Jordan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 22期

关键词：

HipHop-Refine; pseudomonal quorum sensing antagonists; tetravalent lead; phenyl mercuric nitrate; thimerosal;

D O I：

10.1016/j.bmcl.2006.08.069

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

HipHop-Refine was employed to derive a binding hypothesis for pseudomonal quorum sensing (QS) antagonists. The model was employed as 3D search query to screen the National Cancer Institute (NCI) database. One of the hits illustrated nanomolar QS inhibitory activity. The fact that this compound contained tetravalent lead (Pb) prompted us to evaluate the activities of phenyl mercuric nitrate and thimerosal, both fit the binding pharmacophore. The two mercurials illustrated nanomolar to low micromolar IC50 inhibitory values against pseudomonal QS. The three compounds represent a new class of QS inhibitors. (c) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5902 / 5906

页数：5

相关论文

共 40 条

[1]

*ACC SOFTW INC, 2005, CAT US GUID

[2] Identification of common functional configurations among molecules [J].

Barnum, D ;

Greene, J ;

Smellie, A ;

Sprague, P .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1996, 36 (03) :563-571

[3] Quorum sensing and its relevance to infectious diseases [J].

Donabedian, H .

JOURNAL OF INFECTION, 2003, 46 (04) :207-214

[4] Small molecule inhibitors of bacterial quorum sensing and biofilm formation [J].

Geske, GD ;

Wezeman, RJ ;

Siegel, AP ;

Blackwell, HE .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (37) :12762-12763

[5] Pharmacophores incorporating numerous excluded volumes defined by X-ray crystallographic structure in three-dimensional database searching: Application to the thyroid hormone receptor [J].

Greenidge, PA ;

Carlsson, B ;

Bladh, LG ;

Gillner, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (14) :2503-2512

[6] Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound [J].

Hentzer, M ;

Riedel, K ;

Rasmussen, TB ;

Heydorn, A ;

Andersen, JB ;

Parsek, MR ;

Rice, SA ;

Eberl, L ;

Molin, S ;

Hoiby, N ;

Kjelleberg, S ;

Givskov, M .

MICROBIOLOGY-SGM, 2002, 148 :87-102

[7] Methods for the treatment and opinion prevention of bacterial biofilms [J].

Kaplan, JB .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (08) :955-965

[8] A feature based pharmacophore for Candida albicans MyristoylCoA:: protein N-myristoyltransferase inhibitors [J].

Karki, RG ;

Kulkarni, VM .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (02) :147-163

[9] LasR, a transcriptional activator of Pseudomonas aeruginosa virulence genes, functions as a multimer [J].

Kiratisin, P ;

Tucker, KD ;

Passador, L .

JOURNAL OF BACTERIOLOGY, 2002, 184 (17) :4912-4919

[10] Pharmacophore modeling and three-dimensional database searching for drug design using catalyst [J].

Kurogi, Y ;

Güner, OF .

CURRENT MEDICINAL CHEMISTRY, 2001, 8 (09) :1035-1055

← 1 2 3 4 →