title: Ruthenium(II) polypyridyl complex as inhibitor of acetylcholinesterase and Aβ aggregation.
abstract: Two ruthenium(II) polypyridyl complexes [Ru(phen)3](2+) (1) and [Ru(phen)2(bxbg)](2+) (2) (where phen = 1,10 phenanthroline, bxbg = bis(o-xylene)bipyridine glycoluril) have been evaluated for acetylcholinesterase (AChE) and Amyloid-β peptide (Aβ) aggregation inhibition. Complex 2 exhibits higher potency of AChE inhibition and kinetics and molecular modeling studies indicate that ancillary ligand plays significant role in inhibitory potency exhibited by complex 2. The inhibitory effect of these complexes on Aβ (1-40) aggregation is investigated using Thioflavin T fluorescence and Transmission Electron Microscopy. Both complexes efficiently inhibit Aβ (1-40) aggregation and are negligibly toxic to human neuroblastoma cells. This is the first demonstration that ruthenium(II) polypyridyl complexes simultaneously inhibit AChE and Aβ aggregation.
authors.affiliation: Department of Chemistry, University of Pune, Pune 411007, India.
authors.forename: Nilima A
authors.initials: NA
authors.lastname: Vyas
authors.affiliation: Department of Chemistry, University of Pune, Pune 411007, India.
authors.forename: Satish S
authors.initials: SS
authors.lastname: Bhat
authors.affiliation: Department of Chemistry, University of Pune, Pune 411007, India. Electronic address: askum@chem.unipune.ac.in.
authors.forename: Avinash S
authors.initials: AS
authors.lastname: Kumbhar
authors.affiliation: Bioinformatics Group, Centre for Development of Advanced Computing (C-DAC), University of Pune Campus, Pune 411007, India.
authors.forename: Uddhavesh B
authors.initials: UB
authors.lastname: Sonawane
authors.affiliation: Bioinformatics Group, Centre for Development of Advanced Computing (C-DAC), University of Pune Campus, Pune 411007, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Jani
authors.affiliation: Bioinformatics Group, Centre for Development of Advanced Computing (C-DAC), University of Pune Campus, Pune 411007, India.
authors.forename: Rajendra R
authors.initials: RR
authors.lastname: Joshi
authors.affiliation: Biometry and Nutrition Group, Agharkar Research Institute, Pune 411004, India.
authors.forename: Shefali N
authors.initials: SN
authors.lastname: Ramteke
authors.affiliation: Biometry and Nutrition Group, Agharkar Research Institute, Pune 411004, India.
authors.forename: Prasad P
authors.initials: PP
authors.lastname: Kulkarni
authors.affiliation: Biometry and Nutrition Group, Agharkar Research Institute, Pune 411004, India.
authors.forename: Bimba
authors.initials: B
authors.lastname: Joshi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D056831:Coordination Complexes; D009942:Organometallic Compounds; D010618:Phenanthrolines; D011725:Pyridines; C034282:tris-(1,10-phenanthroline)ruthenium; D012428:Ruthenium; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Amyloid-β; Inhibition; Polypyridyl; Ruthenium