Exploiting the lipoic acid structure in the search for novel multitarget ligands against Alzheimer's disease.

Article Details

Citation

Copy to clipboard

Rosini M, Simoni E, Bartolini M, Tarozzi A, Matera R, Milelli A, Hrelia P, Andrisano V, Bolognesi ML, Melchiorre C

Exploiting the lipoic acid structure in the search for novel multitarget ligands against Alzheimer's disease.

Eur J Med Chem. 2011 Nov;46(11):5435-42. doi: 10.1016/j.ejmech.2011.09.001. Epub 2011 Sep 8.

PubMed ID

21924801 [ View in PubMed

]

Abstract

Lipoic acid (LA) is a natural antioxidant. Its structure was previously combined with that of the acetylcholinesterase inhibitor tacrine to give lipocrine (1), a lead compound multitargeted against Alzheimer's disease (AD). Herein, we further explore LA as a privileged structure for developing multimodal compounds to investigate AD. First, we studied the effect of LA chirality by evaluating the cholinesterase profile of 1's enantiomers. Then, a new series of LA hybrids was designed and synthesized by combining racemic LA with motifs of other known anticholinesterase agents (rivastigmine and memoquin). This afforded 4, which represents a step forward in the search for balanced anticholinesterase and antioxidant capacities.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rivastigmine	Acetylcholinesterase	IC 50 (nM)	3030	N/A	N/A	Details