Ruthenium(II) polypyridyl complex as inhibitor of acetylcholinesterase and Aβ aggregation

Nilima A Vyas; Satish S Bhat; Avinash S Kumbhar; Uddhavesh B Sonawane; Vinod Jani; Rajendra R Joshi; Shefali N Ramteke; Prasad P Kulkarni; Bimba Joshi

doi:10.1016/j.ejmech.2014.01.052

Ruthenium(II) polypyridyl complex as inhibitor of acetylcholinesterase and Aβ aggregation

Eur J Med Chem. 2014 Mar 21:75:375-81. doi: 10.1016/j.ejmech.2014.01.052. Epub 2014 Jan 30.

Authors

Nilima A Vyas¹, Satish S Bhat¹, Avinash S Kumbhar², Uddhavesh B Sonawane³, Vinod Jani³, Rajendra R Joshi³, Shefali N Ramteke⁴, Prasad P Kulkarni⁴, Bimba Joshi⁴

Affiliations

¹ Department of Chemistry, University of Pune, Pune 411007, India.
² Department of Chemistry, University of Pune, Pune 411007, India. Electronic address: askum@chem.unipune.ac.in.
³ Bioinformatics Group, Centre for Development of Advanced Computing (C-DAC), University of Pune Campus, Pune 411007, India.
⁴ Biometry and Nutrition Group, Agharkar Research Institute, Pune 411004, India.

PMID: 24556150
DOI: 10.1016/j.ejmech.2014.01.052

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.

Keywords: Acetylcholinesterase; Amyloid-β; Inhibition; Polypyridyl; Ruthenium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / metabolism
Alzheimer Disease / drug therapy
Alzheimer Disease / metabolism
Amyloid beta-Peptides / antagonists & inhibitors*
Amyloid beta-Peptides / metabolism
Amyloid beta-Peptides / ultrastructure
Cell Line, Tumor
Cholinesterase Inhibitors / chemistry*
Cholinesterase Inhibitors / pharmacology*
Coordination Complexes / chemistry*
Coordination Complexes / pharmacology*
Humans
Organometallic Compounds / chemistry
Organometallic Compounds / pharmacology
Phenanthrolines / chemistry
Phenanthrolines / pharmacology
Pyridines / chemistry
Pyridines / pharmacology
Ruthenium / chemistry*
Ruthenium / pharmacology*

Substances

Amyloid beta-Peptides
Cholinesterase Inhibitors
Coordination Complexes
Organometallic Compounds
Phenanthrolines
Pyridines
tris-(1,10-phenanthroline)ruthenium
Ruthenium
Acetylcholinesterase