title: Triaminotriazine DNA helicase inhibitors with antibacterial activity.
abstract: Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB helicase provided a triaminotriazine inhibitor with good antibacterial activity but associated cytotoxicity toward mammalian cells. Synthesis of analogs provided a few inhibitors that retained antibacterial activity and demonstrated a significant reduction in cytotoxicity. The impact of serum and initial investigations toward a mode of action highlight several features of this class of compounds as antibacterials.
authors.affiliation: Targanta Therapeutics Inc., 7170 Frederick Banting, 2nd Floor, St. Laurent, Québec, Canada H4S 2A1.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: McKay
authors.forename: Ranga
authors.initials: R
authors.lastname: Reddy
authors.forename: Francis
authors.initials: F
authors.lastname: Arhin
authors.forename: Adam
authors.initials: A
authors.lastname: Belley
authors.forename: Dario
authors.initials: D
authors.lastname: Lehoux
authors.forename: Greg
authors.initials: G
authors.lastname: Moeck
authors.forename: Ingrid
authors.initials: I
authors.lastname: Sarmiento
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Parr
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.forename: Adel Rafai
authors.initials: AR
authors.lastname: Far
mesh_terms: D000586:Amination; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D014227:Triazines; D004265:DNA Helicases