Pulvinones as bacterial cell wall biosynthesis inhibitors

被引：56

作者：

Antane, S ^{[1
]}

Caufield, CE

Hu, W

Keeney, D

Labthavikul, P

Morris, K

Naughton, SM

Petersen, PJ

Rasmussen, BA

Singh, G

Yang, YJ

机构：

[1] Wyeth Res, Med Chem Chem & Screening Sci, Princeton, NJ 08543 USA

[2] Wyeth Res, Infect Dis, Pearl River, NY 10965 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 01期

关键词：

pulvinones; murein enzyme inhibitors; antibacterial; microwave demethylation;

D O I：

10.1016/j.bmcl.2005.09.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pulvin ones were synthesized (> 180) in arrays and evaluated as inhibitors of early stage cell wall biosynthesis enzymes MurA-MurD. Several pulvinones inhibited Mur enzymes with IC50's in the 1-10 mu g/mL range and demonstrated antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphyloccus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：176 / 180

页数：5

共 20 条

[1]

ANTANE SA, 2004, 228 NAT M AM CHEM SO

[2] Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant Gram-positive bacterial infections [J].

Brickner, SJ ;

Hutchinson, DK ;

Barbachyn, MR ;

Manninen, PR ;

Ulanowicz, DA ;

Garmon, SA ;

Grega, KC ;

Hendges, SK ;

Toops, DS ;

Ford, CW ;

Zurenko, GE .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (03) :673-679

[3] A convergent total synthesis of the michellamines [J].

Bringmann, G ;

Götz, R ;

Keller, PA ;

Walter, R ;

Boyd, MR ;

Lang, FR ;

Garcia, A ;

Walsh, JJ ;

Tellitu, I ;

Bhaskar, KV ;

Kelly, TR .

JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (04) :1090-1097

[4]

BROUWER A, 1995, EUR J PHARM-ENVIRON, V293, P1

[5] New targets and screening approaches in antimicrobial drug discovery [J].

Brown, ED ;

Wright, GD .

CHEMICAL REVIEWS, 2005, 105 (02) :759-774

[6] INTRACELLULAR STEPS OF BACTERIAL-CELL WALL PEPTIDOGLYCAN BIOSYNTHESIS - ENZYMOLOGY, ANTIBIOTICS, AND ANTIBIOTIC-RESISTANCE [J].

BUGG, TDH ;

WALSH, CT .

NATURAL PRODUCT REPORTS, 1992, 9 (03) :199-215

[7]

Campbell A. C., 1985, J CHEM SOC P1, V8, P1567

[8]

Chopra Ian, 2003, Expert Rev Anti Infect Ther, V1, P45, DOI 10.1586/14787210.1.1.45

[9] Structure and function of the Mur enzymes: development of novel inhibitors [J].

El Zoeiby, A ;

Sanschagrin, F ;

Levesque, RC .

MOLECULAR MICROBIOLOGY, 2003, 47 (01) :1-12

[10] Structure-based design approaches to cell wall biosynthesis inhibitors [J].

Katz, AH ;

Caufield, CE .

CURRENT PHARMACEUTICAL DESIGN, 2003, 9 (11) :857-866

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