title: Design and synthesis of 2-aminothiazole based antimicrobials targeting MRSA.
abstract: Privileged structure-based libraries have been shown to provide high affinity lead compounds for a variety of important biological targets. The present study describes the synthesis and screening of a 2-aminothiazole based compound library to determine their utility as antimicrobials, focusing on MRSA. Several of the compounds in this series demonstrated improved antimicrobial activity as compared to ceftriaxone (CTX), a β-lactam antibiotic. The most potent compound (21) had MICs in the range of 2-4 μg/ml across a panel of Staphylococcus aureus strains. In addition, trifluoromethoxy substituted aminothiazoles and aminobenzothiazoles were found to be potent antimicrobials with MICs of 2-16 μg/ml.
authors.affiliation: Temple University School of Pharmacy, Moulder Center for Drug Discovery Research, Philadelphia, PA, USA.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Annadurai
authors.forename: Rogelio
authors.initials: R
authors.lastname: Martinez
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Canney
authors.forename: Tess
authors.initials: T
authors.lastname: Eidem
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dunman
authors.forename: Magid
authors.initials: M
authors.lastname: Abou-Gharbia
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013844:Thiazoles; C004483:2-aminothiazole