Arylthiazole antibiotics targeting intracellular methicillin-resistant Staphylococcus aureus (MRSA) that interfere with bacterial cell wall synthesis

被引：56

作者：

Eid, Islam ^{[1
]}

Elsebaei, Mohamed M. ^{[1
]}

Mohammad, Haroon ^{[2
]}

Hagras, Mohamed ^{[1
]}

Peters, Christine E. ^{[3
]}

Hegazy, Youssef A. ^{[2
]}

Cooper, Bruce ^{[4
]}

Pogliano, Joe ^{[3
]}

Pogliano, Kit ^{[3
]}

Abulkhair, Hamada S. ^{[1
]}

Seleem, Mohamed N. ^{[2
,5
]}

Mayhoub, Abdelrahman S. ^{[1
,6
]}

机构：

[1] Al Azhar Univ, Coll Pharm, Dept Organ Chem, Cairo 11884, Egypt

[2] Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA

[3] Univ Calif San Diego, Div Biol Sci, La Jolla, CA USA

[4] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN USA

[5] Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN USA

[6] Univ Sci & Technol, Biomed Sci, Zewail City Sci & Technol, Giza, Egypt

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 139卷

基金：

美国国家卫生研究院;

关键词：

Antibiotic drug resistance; Caenorhabditis elegans; Methicillin-resistant Staphylococcus aureus MRSA; Intracellular infection; Pharmacokinetics; PHENYLTHIAZOLE ANTIBIOTICS; BACILLUS-SUBTILIS; VANCOMYCIN; ANTIMICROBIALS; INFECTIONS; MECHANISM;

D O I：

10.1016/j.ejmech.2017.08.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The promising antibacterial potency of arylthiazole antibiotics is offset by their limited activity against intracellular bacteria (namely methicillin-resistant Staphylococcus aureus (MRSA)), similar to many clinically-approved antibiotics. The failure to target these hidden pathogens is due to the compounds' lack of proper characteristics to accumulate intracellularly. Fine tuning of the size and polar-surface-area of the linking heteroaromatic ring provided a new series of 5-thiazolylarylthiazoles with balanced properties that allow them to sufficiently cross and accumulate inside macrophages infected with MRSA. The most promising compound 4i exhibited rapid bactericidal activity, good metabolic stability and produced over 80% reduction of intracellular MRSA in infected macrophages. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：665 / 673

页数：9

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