title: Synthesis of 2-pyridyl-benzimidazole iridium(III), ruthenium(II), and platinum(II) complexes. study of the activity as inhibitors of amyloid-β aggregation and neurotoxicity evaluation.
abstract: The design of small molecules that can target the aggregation of Aβ as potential therapeutic agents for Alzheimer's disease is an area of study that has attracted a lot of attention recently. The novel ligand methyl 1-butyl-2-pyridyl-benzimidazole carboxylate was prepared for the synthesis of a series of new iridium(III), ruthenium(II), and platinum(II) 2-pyridyl-benzimidazole complexes. The crystal structure of the half-sandwich iridium(III) complex was established by X-ray diffraction. An arrangement of two cationic complexes in the unit cell is observed, and it seems to be organized by weak π···π interactions that are taking place between two symmetry-related benzimidazole ring systems. All new compounds inhibited aggregation of Aβ1-42 in vitro as shown by both thioflavin T fluorescence assay and transmission electron microscopy. Among them the Ir compound rescued the toxicity of Aβ1-42 in primary cortical neurons effectively.
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence (Campus Mare Nostrum), Universidad de Murcia and Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca , E-30071 Murcia, Spain.
authors.forename: Gorakh S
authors.initials: GS
authors.lastname: Yellol
authors.forename: Jyoti G
authors.initials: JG
authors.lastname: Yellol
authors.forename: Vijaya B
authors.initials: VB
authors.lastname: Kenche
authors.forename: Xiang Ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
authors.forename: Antonio
authors.initials: A
authors.lastname: Donaire
authors.forename: Christoph
authors.initials: C
authors.lastname: Janiak
authors.forename: José
authors.initials: J
authors.lastname: Ruiz
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005260:Female; D007495:Iridium / Q000737:chemistry; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity*; D010984:Platinum / Q000737:chemistry; D011247:Pregnancy; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D012428:Ruthenium / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D001562:Benzimidazoles; D008024:Ligands; D009942:Organometallic Compounds; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D007495:Iridium; D010984:Platinum; D012428:Ruthenium; C031000:benzimidazole