title: Novel compounds targeting bacterial DNA topoisomerase/DNA gyrase.
abstract: Among the targets for the development of new antibacterial agents, bacterial topoisomerases remain a vibrant area of discovery. A structurally diverse set of inhibitors that bind to the adenosine 5'-triphosphate (ATP) site of type II topoisomerases have been disclosed recently. Seven compounds with this mechanism are highlighted, focusing on antibacterial potency and spectrum, as well as examples of in vivo efficacy against pathogens including Staphylococcus aureus and Mycobacterium tuberculosis. Five compounds from two structural classes are exemplified that are inhibitors that bind to the catalytic site of DNA gyrase and topoisomerase IV. The pharmacokinetic and pharmacodynamic properties of these molecules, derived from in vivo efficacy against Gram-positive and Gram-negative pathogens, define the potential for these agents with broad-spectrum and targeted-spectrum clinical utilities.
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. Electronic address: david.ehmann@astrazeneca.com.
authors.forename: David E
authors.initials: DE
authors.lastname: Ehmann
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA.
authors.forename: Sushmita D
authors.initials: SD
authors.lastname: Lahiri
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D026942:DNA Topoisomerases / Q000378:metabolism; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D000255:Adenosine Triphosphate; D026942:DNA Topoisomerases