Targeting methionyl tRNA synthetase: design, synthesis and antibacterial activity against <i>Clostridium difficile</i> of novel 3-biaryl-<i>N</i>-benzylpropan-1-amine derivatives

<p>The synthesis of a series of benzimidazole-<i>N</i>-benzylpropan-1-amines and adenine-<i>N</i>-benzylpropan-1-amines is described. Subsequent evaluation against two strains of the anaerobic bacterium <i>Clostridium difficile</i> was performed with three amine derivatives displaying MIC values of 16 μg/mL. Molecular docking studies of the described amines determined that the amines interact within two active site pockets of <i>C. difficile</i> methionyl tRNA synthetase with methoxy substituents in the benzyl ring and an adenine biaryl moiety resulting in optimal binding interactions.</p>