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

Authors :: Rosini M
Simoni E
Bartolini M
Tarozzi A
Matera R
Milelli A
Hrelia P
Andrisano V
Bolognesi ML
Melchiorre C
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2011 Nov; Vol. 46 (11), pp. 5435-42. Date of Electronic Publication: 2011 Sep 08.
Publication Year :: 2011
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.<br /> (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

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