alexa Hydrophobicity of imidazole derivatives correlates with improved activity against human methanogenic archaea.
Microbiology

Microbiology

Journal of Antivirals & Antiretrovirals

Author(s): Khelaifia S, Brunel JM, Raoult D, Drancourt M

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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. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. This article was published in Int J Antimicrob Agents and referenced in Journal of Antivirals & Antiretrovirals

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