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Targeting methionyl tRNA synthetase: design,synthesis and antibacterial activity against Clostridium difficile of novel 3-biaryl-N-benzylpropan-1-amine derivatives |
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| Authors: | Ahmed G. Eissa James A. Blaxland Rhodri O. Williams Kamel A. Metwally Sobhy M. El-Adl El-Sayed M. Lashine |
| Affiliation: | 1. School of Pharmacy &2. Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff, Wales, UK and;3. Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt;4. Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff, Wales, UK and;5. Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt |
| Abstract: | The synthesis of a series of benzimidazole-N-benzylpropan-1-amines and adenine-N-benzylpropan-1-amines is described. Subsequent evaluation against two strains of the anaerobic bacterium Clostridium difficile 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 C. difficile methionyl tRNA synthetase with methoxy substituents in the benzyl ring and an adenine biaryl moiety resulting in optimal binding interactions. |
| Keywords: | 3-Biaryl-N-benzylpropan-1-amines Clostridium difficile MetRS–ligand interactions methionyl-tRNA synthetase molecular modelling |