ArticleInternational journal of molecular sciences2016
Novel NSAID-Derived Drugs for the Potential Treatment of Alzheimer's Disease.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
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- Exploring the therapeutic potential of cinnamoyl derivatives in attenuating inflammation in lipopolysaccharide-induced Caco-2 cells.Future medicinal chemistry · 2024Article
- Novel styryl-thiazole hybrids as potential anti-Alzheimer's agents.RSC medicinal chemistry · 2023Article
- Flurbiprofen axetil alleviates the effect of formalin-induced inflammatory pain on the cognitive function of rats with mild cognitive impairment through the AMPKα/NF-κB signaling pathway.Annals of translational medicine · 2022Article
- An epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimer's disease.Science translational medicine · 2020Article
- Effect of Novel Pyrrolo[3,4-International journal of molecular sciences · 2020Article
- Network between Cytokines, Cortisol and Occupational Stress in Gas and Oilfield Workers.International journal of molecular sciences · 2020Article
- Insights on the Use of α-Lipoic Acid for Therapeutic Purposes.Biomolecules · 2019Review
- Role of Dietary Supplements in the Management of Parkinson's Disease.Biomolecules · 2019Review
- Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State bothFrontiers in neurology · 2017Article
- Epigenetic Treatment of Neurodegenerative Ophthalmic Disorders: An Eye Toward the Future.BioResearch open access · 2017Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested for the potential treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). Prolonged use of NSAIDs, however, produces gastrointestinal (GI) toxicity. To overcome this serious limitation, the aim of this study was to develop novel NSAID-derived drug conjugates (Anti-inflammatory-Lipoyl derivatives, AL4-9) that preserve the beneficial effects of NSAIDS without causing GI problems. As such, we conjugated selected well-known NSAIDs, such as (S)-naproxen and (R)-flurbiprofen, with (R)-α-lipoic acid (LA) through alkylene diamine linkers. The selection of the antioxidant LA was based on the proposed role of oxidative stress in the development and/or progression of AD. Our exploratory studies revealed that AL7 containing the diaminoethylene linker between (R)-flurbiprofen and LA had the most favorable chemical and in vitro enzymatic stability profiles among the synthesized compounds. Upon pretreatment, this compound exhibited excellent antioxidant activity in phorbol 12-miristate 13-acetate (PMA)-stimulated U937 cells (lymphoblast lung from human) and Aβ(25-35)-treated THP-1 cells (leukemic monocytes). Furthermore, AL7 also modulated the expression of COX-2, IL-1β and TNF-α in these cell lines, suggesting anti-inflammatory activity. Taken together, AL7 has emerged as a potential lead worthy of further characterization and testing in suitable in vivo models of AD.
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