Peptide deformylase inhibitors with retro-amide scaffold: Synthesis and structure-activity relationships

被引：11

作者：

Lee, Seung Kyu ^{[1
,4
]}

Choi, Kwang Hyun ^{[1
]}

Lee, Sang Jae ^{[1
]}

Suh, Se Won ^{[2
]}

Kim, B. Moon ^{[3
]}

Lee, Bong Jin ^{[1
,4
]}

机构：

[1] Seoul Natl Univ, Coll Pharm, Promeditech Ltd, Seoul 151742, South Korea

[2] Seoul Natl Univ, Coll Nat Sci, Dept Biophys & Chem Biol, Seoul 151742, South Korea

[3] Seoul Natl Univ, Coll Nat Sci, Dept Chem, Seoul 151742, South Korea

[4] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 15期

关键词：

PDF; SAR; Antibacterial; Retro-amide; ACTINONIN; POTENT; AGENTS; ESTERS;

D O I：

10.1016/j.bmcl.2010.06.088

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Peptide deformylase (PDF) is a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins. Thus inhibition of PDF activity is considered to be one of the most effective antibiotic strategies. Reported herein are the synthesis and structure-activity relationship studies of retro-amide inhibitors based on actinonin, a naturally occurring PDF inhibitor. Analysis of the structure-activity relationships led to the discovery of 7a, which exhibits potent enzyme inhibition and antibacterial activity against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4317 / 4319

页数：3

共 14 条

[1] 2-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)- and 2-(2,2-dioxo-1,4-dihydro-2H-2λ6-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamides as potent and selective peptide deformylase inhibitors [J].

Apfel, C ;

Banner, DW ;

Bur, D ;

Dietz, M ;

Hubschwerlen, C ;

Locher, H ;

Marlin, F ;

Masciadri, R ;

Pirson, W ;

Stalder, H .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (12) :1847-1852

[2] An efficient new protocol for the formation of unsymmetrical tri- and tetrasubstituted ureas [J].

Batey, RA ;

Santhakumar, V ;

Yoshina-Ishii, C ;

Taylor, SD .

TETRAHEDRON LETTERS, 1998, 39 (35) :6267-6270

[3] Therapeutic potential of peptide deformylase inhibitors [J].

Chen, D ;

Yuan, Z .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2005, 14 (09) :1107-1116

[4] Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor [J].

Chen, DZ ;

Patel, DV ;

Hackbarth, CJ ;

Wang, W ;

Dreyer, G ;

Young, DC ;

Margolis, PS ;

Wu, C ;

Ni, ZJ ;

Trias, J ;

White, RJ ;

Yuan, ZY .

BIOCHEMISTRY, 2000, 39 (06) :1256-1262

[5] ACTINONIN - AN ANTIBIOTIC SUBSTANCE PRODUCED BY AN ACTINOMYCETE [J].

GORDON, JJ ;

MILLER, GA ;

KELLY, BK .

NATURE, 1962, 195 (4842) :701-&

[6] The crystal structures of four peptide deformylases bound to the antibiotic actinonin reveal two distinct types: A platform for the structure-based design of antibacterial agents [J].

Guilloteau, JP ;

Mathieu, M ;

Giglione, C ;

Blanc, V ;

Dupuy, A ;

Chevrier, M ;

Gil, P ;

Famechon, A ;

Meinnel, T ;

Mikol, V .

JOURNAL OF MOLECULAR BIOLOGY, 2002, 320 (05) :951-962

[7]

Johnson K. W., 2005, Current Drug Targets - Infectious Disorders, V5, P39, DOI 10.2174/1568005053174618

[8]

LIPINSKY CA, 1989, ANN REPT MED CHEM, V32, P2493

[9] A survey of polypeptide deformylase function throughout the eubacterial lineage [J].

Mazel, D ;

Coic, E ;

Blanchard, S ;

Saurin, W ;

Marliere, P .

JOURNAL OF MOLECULAR BIOLOGY, 1997, 266 (05) :939-949

[10] A CONVENIENT PROCEDURE FOR THE PREPARATION OF AMINO-ACID HYDROXAMATES FROM ESTERS [J].

PIRRUNG, MC ;

CHAU, JHL .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (24) :8084-8085

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