title: In vitro activities of three new dihydrofolate reductase inhibitors against clinical isolates of gram-positive bacteria.
abstract: BAL0030543, BAL0030544, and BAL0030545 are dihydrophthalazine inhibitors with in vitro potency against gram-positive pathogens. The MIC(50)s for methicillin (meticillin)-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, hetero-vancomycin-resistant Staphylococcus aureus, and vancomycin-resistant Staphylococcus aureus (VISA) range from 0.015 to 0.25 microg/ml (MIC(90)s < or = 0.5 microg/ml). MIC(50)s for beta-hemolytic streptococci range from 0.03 to 0.06 microg/ml, MIC(50)s for Streptococcus pneumoniae range from 0.06 to 0.12 microg/ml, MIC(50)s for Listeria monocytogenes range from 0.015 to 0.06 microg/ml, and MIC(50)s for Streptococcus mitis are < or = 0.015 microg/ml. These three dihydrophthalazine antifolates have improved potency compared to that of trimethoprim and activity against gram-positive pathogens resistant to other drug classes. (This work was presented in part at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2008.).
authors.affiliation: BCARE, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, United Kingdom. karen.bowker@nbt.nhs.uk
authors.forename: Karen E
authors.initials: KE
authors.lastname: Bowker
authors.forename: Patrick
authors.initials: P
authors.lastname: Caspers
authors.forename: Bérengère
authors.initials: B
authors.lastname: Gaucher
authors.forename: Alasdair P
authors.initials: AP
authors.lastname: MacGowan
mesh_terms: D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010793:Phthalazines / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects
chemical_list: C546920:BAL 0030543; C546921:BAL 0030544; C546922:BAL 0030545; D005493:Folic Acid Antagonists; D010793:Phthalazines