title: Hydrophobicity of imidazole derivatives correlates with improved activity against human methanogenic archaea.
abstract: Methanogenic archaea are involved in periodontitis in humans. They have also been implicated in digestive tract pathologies and obesity. These microorganisms are broadly resistant to antibiotics, except for metronidazole and ornidazole. In this study, eight imidazole derivatives were synthesised and their in vitro cytotoxicity and activity against six species of methanogenic archaea, including Methanobrevibacter smithii, Methanobrevibacter oralis, Methanosphaera stadtmanae, Methanobacterium beijingense, Methanosaeta concilii and Methanomassiliicoccus luminyensis, were tested. Whilst the effective half-maximum cytotoxic concentrations (EC50 values) of all compounds were ≤50 mg/L, minimum inhibitory concentrations (MICs) were 0.05-0.8 mg/L for most methanogenic archaea and 0.1-1mg/L for M. stadtmanae. These results indicated a >20-400 therapeutic index (EC50/MIC) for these compounds, which compared with metronidazole exhibited 1-log increased activity against methanogenic archaea cultured from the human microbiota. These compounds are therefore promising molecules for the treatment of methanogenic archaea-related infections.
authors.affiliation: Unité de recherche sur les maladies infectieuses et tropicales émergentes, UMR CNRS 6236 IRD 3R198, FR IDMM, Méditerranée Infection, Aix-Marseille Université, Marseille, France.
authors.forename: Saber
authors.initials: S
authors.lastname: Khelaifia
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Brunel
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.forename: Michel
authors.initials: M
authors.lastname: Drancourt
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001105:Archaea / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008697:Methane / Q000378:metabolism; D008826:Microbial Sensitivity Tests
chemical_list: D000890:Anti-Infective Agents; D007093:Imidazoles; C029899:imidazole; D008697:Methane