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Synthesis and biological activity of new phthalimides as potential anti-inflammatory agents.
- Source :
-
Bioorganic & Medicinal Chemistry . Jul2017, Vol. 25 Issue 13, p3396-3405. 10p. - Publication Year :
- 2017
-
Abstract
- The overproduction of nitric oxide (NO) plays an important role in a variety of pathophysiological processes, including inflammation. Therefore, the suppression of NO production is a promising target in the design of anti-inflammatory agents. In the present study, a series of phthalimide analogs was synthesized, and their anti-inflammatory activities were evaluated using lipopolysaccharide (LPS)-stimulated NO production in cultured murine macrophage RAW264.7 cells. A structure-activity relationship study showed that the free hydroxyl group at C-4 and C-6 and the bulkiness of the N -substituted alkyl chain are associated with biological activity. Among the series of phthalimide derivatives, compound IIh exhibited potent inhibitory activity, with an IC 50 value of 8.7 µg/mL. Further study revealed that the inhibitory activity of compound IIh was correlated with the down-regulation of the mRNA and protein expression of LPS-stimulated inducible nitric oxide synthase (iNOS). Compound IIh also suppressed the induction of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β in LPS-stimulated RAW 264.7 cells. The anti-inflammatory activity of compound IIh was also found to be associated with the suppression of the Toll-like receptor (TLR)4 signaling pathway by down-regulating the activation of interferon regulatory factor 3 (IRF-3) and interferon-β and signal transducer expression. These findings demonstrate that novel phthalimides might be potential candidates for the development of anti-inflammatory agents. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09680896
- Volume :
- 25
- Issue :
- 13
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 123217376
- Full Text :
- https://doi.org/10.1016/j.bmc.2017.04.027