Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents
Article
Li, Y, Bionda, N, Fleeman, R et al. (2016). Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents
. BIOORGANIC & MEDICINAL CHEMISTRY, 24(21), 5633-5638. 10.1016/j.bmc.2016.09.027
Li, Y, Bionda, N, Fleeman, R et al. (2016). Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents
. BIOORGANIC & MEDICINAL CHEMISTRY, 24(21), 5633-5638. 10.1016/j.bmc.2016.09.027
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 MIC90value of 3.7 μg/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.
