title: Targeting methionyl tRNA synthetase: design, synthesis and antibacterial activity against Clostridium difficile of novel 3-biaryl-N-benzylpropan-1-amine derivatives.
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.
authors.affiliation: a School of Pharmacy & Pharmaceutical Sciences, Cardiff University , King Edward VII Avenue, Cardiff, Wales , UK and.|b Department of Medicinal Chemistry , Faculty of Pharmacy, Zagazig University , Zagazig , Egypt.
authors.forename: Ahmed G
authors.initials: AG
authors.lastname: Eissa
authors.affiliation: a School of Pharmacy & Pharmaceutical Sciences, Cardiff University , King Edward VII Avenue, Cardiff, Wales , UK and.
authors.forename: James A
authors.initials: JA
authors.lastname: Blaxland
authors.affiliation: a School of Pharmacy & Pharmaceutical Sciences, Cardiff University , King Edward VII Avenue, Cardiff, Wales , UK and.
authors.forename: Rhodri O
authors.initials: RO
authors.lastname: Williams
authors.affiliation: b Department of Medicinal Chemistry , Faculty of Pharmacy, Zagazig University , Zagazig , Egypt.
authors.forename: Kamel A
authors.initials: KA
authors.lastname: Metwally
authors.affiliation: b Department of Medicinal Chemistry , Faculty of Pharmacy, Zagazig University , Zagazig , Egypt.
authors.forename: Sobhy M
authors.initials: SM
authors.lastname: El-Adl
authors.affiliation: b Department of Medicinal Chemistry , Faculty of Pharmacy, Zagazig University , Zagazig , Egypt.
authors.forename: El-Sayed M
authors.initials: el-SM
authors.lastname: Lashine
authors.affiliation: a School of Pharmacy & Pharmaceutical Sciences, Cardiff University , King Edward VII Avenue, Cardiff, Wales , UK and.
authors.forename: Leslie W J
authors.initials: LW
authors.lastname: Baillie
authors.affiliation: a School of Pharmacy & Pharmaceutical Sciences, Cardiff University , King Edward VII Avenue, Cardiff, Wales , UK and.
authors.forename: Claire
authors.initials: C
authors.lastname: Simons
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016360:Clostridioides difficile / Q000187:drug effects*; D015195:Drug Design; D008718:Methionine-tRNA Ligase / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D008718:Methionine-tRNA Ligase; D011407:Propane
keywords: 3-Biaryl-N-benzylpropan-1-amines; Clostridium difficile; MetRS–ligand interactions; methionyl-tRNA synthetase; molecular modelling