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Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents.

ABSTRACT: In an effort to develop novel antimicrobial agents against drug-resistant bacterial infections, 5,6-dihydroimidazo[2,1-b]thiazole compounds were synthesized and tested for their antimicrobial activity. Eight compounds comprised by two sub-scaffolds were identified as hits against methicillin-resistant Staphylococcus aureus (MRSA). These hits were modified at 6-position by replacing (S)-6 to (R)-6 configuration and the (R)-isomers increased their antimicrobial activities by two-fold. The most active compound showed a MIC90 value of 3.7?g/mL against MRSA in a standard microdilution bacterial growth inhibitory assay. This compound protected wax moth worms against MRSA at a dose of 5× MIC using a worm infectious model. This compound also exhibited inhibition of DNA gyrase activity in a DNA gyrase supercoil assay, suggesting the 5,6-dihydroimidazo[2,1-b]thiazoles may target DNA gyrase for the antimicrobial action.

SUBMITTER: Li Y

PROVIDER: S-EPMC5065789 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents.

Li Yangmei Y Bionda Nina N Fleeman Renee R Wang Hongjie H Ozawa Akihiko A Houghten Richard A RA Shaw Lindsey L

Bioorganic & medicinal chemistry 20160912 21

In an effort to develop novel antimicrobial agents against drug-resistant bacterial infections, 5,6-dihydroimidazo[2,1-b]thiazole compounds were synthesized and tested for their antimicrobial activity. Eight compounds comprised by two sub-scaffolds were identified as hits against methicillin-resistant Staphylococcus aureus (MRSA). These hits were modified at 6-position by replacing (S)-6 to (R)-6 configuration and the (R)-isomers increased their antimicrobial activities by two-fold. The most act ...[more]

PMID: 27663549

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