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.
MeSH terms
-
Amination
-
Animals
-
Anti-Bacterial Agents / chemical synthesis*
-
Anti-Bacterial Agents / chemistry
-
Anti-Bacterial Agents / pharmacology*
-
Anti-Bacterial Agents / toxicity
-
Cell Line
-
DNA Helicases / antagonists & inhibitors*
-
DNA Helicases / metabolism
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology
-
Enzyme Inhibitors / toxicity
-
Escherichia coli / drug effects
-
Escherichia coli / enzymology
-
Humans
-
Microbial Sensitivity Tests
-
Molecular Structure
-
Pseudomonas aeruginosa / drug effects
-
Pseudomonas aeruginosa / enzymology
-
Staphylococcus aureus / drug effects
-
Staphylococcus aureus / enzymology
-
Structure-Activity Relationship
-
Triazines / chemical synthesis
-
Triazines / chemistry*
-
Triazines / pharmacology*
-
Triazines / toxicity
Substances
-
Anti-Bacterial Agents
-
Enzyme Inhibitors
-
Triazines
-
DNA Helicases