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