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. 2016;7(10):1952-1956.
doi: 10.1039/C6MD00365F. Epub 2016 Jul 27.

Potentiation of the Fosmidomycin analogue FR 900098 with substituted 2-oxazolines against Francisella novicida

Matthew D Stephens  1 , Nisakorn Yodsanit  2 , Christian Melander  1
Affiliations

Potentiation of the Fosmidomycin analogue FR 900098 with substituted 2-oxazolines against Francisella novicida

Matthew D Stephens et al. Medchemcomm. 2016.

Abstract

A library of 33 compounds was screened for potentiation of the antibiotic FR 900098 against the Francisella tularensis surrogate Francisella novicida. From the screen a highly potent 2-oxazoline adjuvant was discovered capable of potentiating FR 900098 with a 1000-fold reduction in MIC against the Francisella sub-species F. novicida and F. philomiragia.

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Conflict of interest statement

† The authors declare no competing interests.

Figures

Figure 1
Figure 1
Structures of the lead compound and antibiotic. Values in red are MIC value of compound or antibiotic. Value in blue is MIC of antibiotic in the presence of 1a against F. philomiragia.
Figure 2
Figure 2
Analogue library. Compounds were tested at 25% of their MIC value. Values in red are MIC value of compound or antibiotic. Values in blue are MIC of antibiotic in presence of compound against F. novicida. aCompound was tested at 40 μM.
Scheme 1
Scheme 1
General synthetic scheme for cyclization of oxazolines.
Scheme 2
Scheme 2
Synthetic route to oxazolines 1i and 1j.
Scheme 3
Scheme 3
Synthetic route for aryl head analogues.
Scheme 4
Scheme 4
Synthetic route to thiazolines.
Scheme 5
Scheme 5
Synthetic route toward imidazoles and acetals.
Scheme 6
Scheme 6
Synthesis of the carboxylic acid (8) and methyl ester (9).
See this image and copyright information in PMC

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