title: Ruthenium(II) polypyridyl complexes with hydrophobic ancillary ligand as Aβ aggregation inhibitors.
abstract: The synthesis, spectral and electrochemical characterization of the complexes of the type [Ru(NN)2(txbg)](2+) where NN is 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), dipyrido [3,2-d:2',3f] quinoxaline (dpq) (3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz) (4) which incorporate the tetra-xylene bipyridine glycoluril (txbg) as the ancillary ligand are described in detail. Crystal structures of ligand txbg and complex 2 were solved by single crystal X-ray diffraction. Thioflavin T (ThT) fluorescence and Transmission Electron Microscopy (TEM) results indicated that at micromolar concentration all complexes exhibit significant potential of Aβ aggregation inhibition, while the ligand txbg displayed weak activity towards Aβ aggregation. Complex 1 showed relatively low inhibition (70%) while complexes 2-4 inhibited nearly 100% Aβ aggregation after 240 h of incubation. The similar potential of complexes 2-4 and absence of any trend in their activity with the planarity of polypyridyl ligands suggests there is no marked effect of planarity of coligands on their inhibitory potential. Further studies on acetylcholinesterase (AChE) inhibition indicated very weak activity of these complexes against AChE. Detailed interactions of Aβ with both ligand and complex 2 have been studied by molecular modeling. Complex 2 showed interactions involving all three polypyridyl ligands with hydrophobic region of Aβ. Furthermore, the toxicity of these complexes towards human neuroblastoma cells was evaluated by MTT assay and except complex 4, the complexes displayed very low toxicity.
authors.affiliation: Department of Chemistry, Savitribai Phule Pune University, Pune, 411007, India.
authors.forename: Nilima A
authors.initials: NA
authors.lastname: Vyas
authors.affiliation: Bioprospecting, Agharkar Research Institute, Pune, 411004, India.
authors.forename: Shefali N
authors.initials: SN
authors.lastname: Ramteke
authors.affiliation: Department of Chemistry, Savitribai Phule Pune University, Pune, 411007, India. Electronic address: askum@chem.unipune.ac.in.
authors.forename: Avinash S
authors.initials: AS
authors.lastname: Kumbhar
authors.affiliation: Bioprospecting, Agharkar Research Institute, Pune, 411004, India.
authors.forename: Prasad P
authors.initials: PP
authors.lastname: Kulkarni
authors.affiliation: Bioinformatics Group, Centre for Development of Advanced Computing (C-DAC), Savitribai Phule Pune University, Pune, 411007, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Jani
authors.affiliation: Bioinformatics Group, Centre for Development of Advanced Computing (C-DAC), Savitribai Phule Pune University, 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), Savitribai Phule Pune University, Pune, 411007, India.
authors.forename: Rajendra R
authors.initials: RR
authors.lastname: Joshi
authors.affiliation: Bioprospecting, Agharkar Research Institute, Pune, 411004, India.
authors.forename: Bimba
authors.initials: B
authors.lastname: Joshi
authors.affiliation: School of Chemistry, National University of Ireland, Galway, Ireland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Erxleben
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000480:Alkynes / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry*; D066329:Protein Aggregates / Q000187:drug effects*; D011487:Protein Conformation; D012428:Ruthenium / Q000737:chemistry*; D006574:Heterocyclic Compounds, 2-Ring; D048289:Imidazolidines
chemical_list: D000110:Acetylcholinesterase; D000480:Alkynes; D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D007093:Imidazoles; D008024:Ligands; D009942:Organometallic Compounds; D010446:Peptide Fragments; D066329:Protein Aggregates; D012428:Ruthenium; C078592:amyloid beta-protein (1-40); C092018:glycoluril; D006574:Heterocyclic Compounds, 2-Ring; D048289:Imidazolidines
keywords: Acetylcholinesterase; Amyloid beta inhibition; Hydrophobic ligand; Ru(II) polypyridyl complexes