Triaminotriazine DNA helicase inhibitors with antibacterial activity

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.

Graphical abstractThe structure–activity relationships around a Pseudomonas aeruginosa DNA helicase triaminotriazine inhibitor in terms of inhibitory and antibacterial activities as well as cytotoxicity toward mammalian cells are presented. Several features of this class of compounds as antibacterials are highlighted.Figure optionsDownload full-size imageDownload as PowerPoint slide