An evolved oxazolidinone with selective potency against Mycobacterium tuberculosis and gram positive bacteria

被引：7

作者：

Kaushik, Amit ^{[1
,2
]}

Heuer, Abigail M. ^{[3
]}

Bell, Drew T. ^{[1
,2
]}

Culhane, Jeffrey C. ^{[3
]}

Ebner, David C. ^{[3
]}

Parrish, Nicole ^{[4
]}

Ippoliti, J. Thomas ^{[3
]}

Lamichhane, Gyanu ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Taskforce Study Resistance Emergence & Antimicrob, 1550 Orleans St, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Ctr TB Res, Dept Med, 1550 Orleans St, Baltimore, MD 21287 USA

[3] Univ St Thomas, Dept Chem, St Paul, MN 55105 USA

[4] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 15期

关键词：

Antimicrobials; Oxazolidinone; Mycobacterium tuberculosis; Staphylococcus aureus; E; faecalis; EXTENSIVELY DRUG-RESISTANT; INFECTIOUS-DISEASES-SOCIETY; IN-VITRO ACTIVITIES; MDR-TB; SAFETY; EFFICACY; TOLERABILITY; PNU-100480; TIME;

D O I：

10.1016/j.bmcl.2016.06.019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Innovation of new antibacterials that are effective against strains that have developed resistance to existing drugs would strengthen our ability to treat and subsequently control spread of pathogenic bacteria. Increasing incidence of infections with drug resistant bacteria has become a common occurrence in recent times. We have developed an evolved oxazolidinone, T145, which inhibits growth of Enterococcus faecalis, Staphylococcus aureus and Mycobacterium tuberculosis (Mtb) with sub mu g/ml potencies that are potentially therapeutically valuable. The oxazolidinone is bactericidal against Mtb but bacteriostatic against E. faecalis and S. aureus. In addition to therapeutically valuable potency and bactericidal activity against Mtb, T145 minimizes selection of spontaneous resistant mutants, a trait that prolongs longevity of a drug in clinical use. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：3572 / 3576

页数：5

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