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1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics against Multidrug-Resistant Acinetobacter baumannii.


ABSTRACT: With only two new classes of antibiotics developed in the last 40 years, novel antibiotics are desperately needed to combat the growing problem of multidrug-resistant and extensively drug resistant bacteria, particularly Gram-negative bacteria. Described in this letter is the synthesis and antibiotic activity of 1,2,4-triazolidine-3-thiones as narrow spectrum antibiotics. Optimization of the 1,2,4-triazolidine-3-thione scaffold identified a small molecule with potent antibiotic activity against multiple strains of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii. This small molecule also shows single dose, in vivo activity in a Galleria mellonella infection model with A. baumannii and represents a promising start in the development of a class of drugs that can target this bacterial pathogen.

SUBMITTER: Huggins WM 

PROVIDER: S-EPMC5238477 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics against Multidrug-Resistant <i>Acinetobacter baumannii</i>.

Huggins William M WM   Minrovic Bradley M BM   Corey Brendan W BW   Jacobs Anna C AC   Melander Roberta J RJ   Sommer Roger D RD   Zurawski Daniel V DV   Melander Christian C  

ACS medicinal chemistry letters 20161112 1


With only two new classes of antibiotics developed in the last 40 years, novel antibiotics are desperately needed to combat the growing problem of multidrug-resistant and extensively drug resistant bacteria, particularly Gram-negative bacteria. Described in this letter is the synthesis and antibiotic activity of 1,2,4-triazolidine-3-thiones as narrow spectrum antibiotics. Optimization of the 1,2,4-triazolidine-3-thione scaffold identified a small molecule with potent antibiotic activity against  ...[more]

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