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

Amit Kaushik; Abigail M. Heuer; Drew T. Bell; Jeffrey C. Culhane; David C. Ebner; Nicole Parrish; J. Thomas Ippoliti; Gyanu Lamichhane

doi:10.1016/j.bmcl.2016.06.019

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

Amit Kaushik, Abigail M. Heuer, Drew T. Bell, Jeffrey C. Culhane, David C. Ebner, Nicole Parrish, J. Thomas Ippoliti, Gyanu Lamichhane

School of Medicine

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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 μg/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.

Original language	English (US)
Pages (from-to)	3572-3576
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2016.06.019
State	Published - 2016

Keywords

Antimicrobials
E. faecalis
Mycobacterium tuberculosis
Oxazolidinone
Staphylococcus aureus

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2016.06.019

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title = "An evolved oxazolidinone with selective potency against Mycobacterium tuberculosis and gram positive bacteria",

abstract = "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 μg/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.",

keywords = "Antimicrobials, E. faecalis, Mycobacterium tuberculosis, Oxazolidinone, Staphylococcus aureus",

author = "Amit Kaushik and Heuer, {Abigail M.} and Bell, {Drew T.} and Culhane, {Jeffrey C.} and Ebner, {David C.} and Nicole Parrish and Ippoliti, {J. Thomas} and Gyanu Lamichhane",

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AU - Kaushik, Amit

AU - Heuer, Abigail M.

AU - Bell, Drew T.

AU - Culhane, Jeffrey C.

AU - Ebner, David C.

AU - Parrish, Nicole

AU - Ippoliti, J. Thomas

AU - Lamichhane, Gyanu

PY - 2016

Y1 - 2016

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AB - 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 μg/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.

KW - Antimicrobials

KW - E. faecalis

KW - Mycobacterium tuberculosis

KW - Oxazolidinone

KW - Staphylococcus aureus

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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