Identification of 5, 6-dihydroimidazo[2, 1-b]thiazoles as a new class of antimicrobial agents. Issue 21 (1st November 2016)

• Record Type: Journal Article
• Authors: Li, Yangmei; Bionda, Nina; Fleeman, Renee; Wang, Hongjie; Ozawa, Akihiko; Houghten, Richard A.; Shaw, Lindsey
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 21(2016)
• Page Start: 5633
• Page End: 5638
• Publication Date: 2016-11-01
• Subjects: Heterocyclic -- Antimicrobial -- MRSA -- DNA gyrase -- Imidazothiazole; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.09.027
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 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.