title: Antibacterial activity of head-to-head bis-benzimidazoles.
abstract: Symmetric bis-benzimidazole (BBZ) conjugates were profiled for activity against a range of Gram-positive and Gram-negative bacteria. para-Substituted ethoxy, amino and methoxy derivatives displayed potent bacteriostatic activity against meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, streptococci and Listeria monocytogenes. Moderate to good activity was also found against mycobacteria; two compounds were strongly active against logarithmic phase and hypoxia-induced latent Mycobacterium tuberculosis. No compound displayed significant activity towards Gram-negative bacteria. Only high concentrations of antibacterial BBZs showed cytotoxic effects towards fibroblasts, and the most active compound was well tolerated by zebrafish embryos.
authors.affiliation: School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Joao B
authors.initials: JB
authors.lastname: Moreira
authors.forename: John
authors.initials: J
authors.lastname: Mann
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
authors.forename: Timothy D
authors.initials: TD
authors.lastname: McHugh
authors.forename: Peter W
authors.initials: PW
authors.lastname: Taylor
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D001562:Benzimidazoles
keywords: Antibacterial bis-benzimidazoles; Gram-positive pathogens; Mycobacterium tuberculosis; Staphylococcus aureus