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Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity.
Arch Pharm (Weinheim). 2010 Mar; 343(3):133-42.AP

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.

Authors+Show Affiliations

Dipartimento di Scienze del Farmaco, Università G. D'Annunzio, Chieti, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20186865

Citation

Sozio, Piera, et al. "Ibuprofen and Lipoic Acid Diamides as Potential Codrugs With Neuroprotective Activity." Archiv Der Pharmazie, vol. 343, no. 3, 2010, pp. 133-42.
Sozio P, D'Aurizio E, Iannitelli A, et al. Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity. Arch Pharm (Weinheim). 2010;343(3):133-42.
Sozio, P., D'Aurizio, E., Iannitelli, A., Cataldi, A., Zara, S., Cantalamessa, F., Nasuti, C., & Di Stefano, A. (2010). Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity. Archiv Der Pharmazie, 343(3), 133-42. https://doi.org/10.1002/ardp.200900152
Sozio P, et al. Ibuprofen and Lipoic Acid Diamides as Potential Codrugs With Neuroprotective Activity. Arch Pharm (Weinheim). 2010;343(3):133-42. PubMed PMID: 20186865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity. AU - Sozio,Piera, AU - D'Aurizio,Eleonora, AU - Iannitelli,Antonio, AU - Cataldi,Amelia, AU - Zara,Susi, AU - Cantalamessa,Franco, AU - Nasuti,Cinzia, AU - Di Stefano,Antonio, PY - 2010/2/27/entrez PY - 2010/2/27/pubmed PY - 2010/7/8/medline SP - 133 EP - 42 JF - Archiv der Pharmazie JO - Arch Pharm (Weinheim) VL - 343 IS - 3 N2 - 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. SN - 1521-4184 UR - https://www.unboundmedicine.com/medline/citation/20186865/Ibuprofen_and_lipoic_acid_diamides_as_potential_codrugs_with_neuroprotective_activity_ L2 - https://doi.org/10.1002/ardp.200900152 DB - PRIME DP - Unbound Medicine ER -