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Discovery and evaluation of novel anti-inflammatory derivatives of natural bioactive curcumin.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2014 Nov 04; Vol. 8, pp. 2161-71. Date of Electronic Publication: 2014 Nov 04 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Curcumin is a natural active product that has various pharmacological activities such as anti-inflammatory effects. Here, we report the synthesis and evaluation of 34 monocarbonyl curcumin analogs as novel anti-inflammatory agents. Among the analogs, the symmetrical heterocyclic type displayed the strongest inhibition of lipopolysaccharide (LPS)-stimulated expression of pro-inflammatory cytokines in macrophages. Analogs S1-S5 and AS29 reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production in a dose-dependent manner and also displayed excellent stability and low cytotoxicity in vitro. In addition, analog S1 dose-dependently inhibited LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, analogs S1 and S4 displayed a significant protective effect on LPS-induced septic death in mouse models, with 40% and 50% survival rates, respectively. These data demonstrate that the heterocyclic monocarbonyl curcumin analogs have potential therapeutic effects in acute inflammatory diseases.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal chemistry
Biological Products chemical synthesis
Biological Products chemistry
Cell Line
Curcumin chemical synthesis
Curcumin chemistry
Cytokines antagonists & inhibitors
Cytokines biosynthesis
Dose-Response Relationship, Drug
Humans
Lipopolysaccharides administration & dosage
Lipopolysaccharides antagonists & inhibitors
Lipopolysaccharides pharmacology
Macrophages drug effects
Male
Mice
Mice, Inbred C57BL
Molecular Structure
Shock, Septic drug therapy
Structure-Activity Relationship
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Biological Products pharmacology
Curcumin pharmacology
Drug Discovery
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 25395833
- Full Text :
- https://doi.org/10.2147/DDDT.S69914