UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity.

Sozio, P; D'Aurizio, E; Iannitelli, A; Cataldi, A; Zara, S; Cantalamessa, F; Nasuti, C; (2010) Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity. Arch Pharm (Weinheim) , 343 (3) pp. 133-142. 10.1002/ardp.200900152.

Full text not available from this repository.

Abstract

Current evidences support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease (AD). In the present work, our attention was focused on ibuprofen (IBU) used in clinical trails to prevent Alzheimer's disease, and (R)-alpha-lipoic acid (LA) considered as a potential neuroprotective agent in AD therapy. In particular, we investigated a series of lipophilic molecular combinations obtained by joining (R)-alpha-lipoic acid and ibuprofen via an amide bond. These new entities might allow targeted delivery of the parent drugs to neurons, where cellular oxidative stress and inflammation seem related to Alzheimer's disease. Our study included the synthesis of conjugates 1-3 and the evaluation of their physicochemical and in-vitro antioxidant properties. The new compounds are extremely stable in aqueous buffer solutions (pH = 1.3 and 7.4), and in rat and human plasma they showed a slow bioconversion to ibuprofen and (R)-alpha-lipoic acid. Codrugs 1-3 displayed in vitro free radical scavenging activity and were hydrolyzed more rapidly in brain tissue than in rat serum indicating that these new entities might allow targeted delivery of the parent drugs to neurons. The immunohistochemical analysis of Abeta (1-40) protein showed that Abeta-injected cerebral cortices treated with ibuprofen or compound 1 showed few plaques within capillary vessels and, in particular, Abeta (1-40) protein was less expressed in codrug-1-treated than in ibuprofen-treated cerebral cortex.

Type: Article
Title: Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity.
Location: Germany
DOI: 10.1002/ardp.200900152
Keywords: Alzheimer Disease, Amyloid beta-Peptides, Animals, Anti-Inflammatory Agents, Non-Steroidal, Antioxidants, Brain, Chemistry, Pharmaceutical, Diamide, Disease Models, Animal, Drug Combinations, Drug Stability, Free Radical Scavengers, Ibuprofen, Male, Neuroprotective Agents, Prodrugs, Rats, Rats, Wistar, Thioctic Acid
URI: http://discovery.ucl.ac.uk/id/eprint/1377569
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item