Total Synthesis and Anti-inflammatory Evaluation of Penchinone A and Its Structural Analogues.
Yongguk OhYeon Jeong JangMijin JeonHyung Sik KimJong-Hwan KwakKyu Hyuck ChungSuhkneung PyoYoung Hoon JungIn Su KimPublished in: The Journal of organic chemistry (2018)
The first total synthesis and biological evaluation of penchinone A and its structural analogues are described. The key steps for the preparation of penchinone A derivatives involve the oxime-directed palladium(II)-catalyzed oxidative acylation, Claisen rearrangement, and base-mediated olefin migration. This transformation efficiently provides a range of allyl-substituted biaryl ketones with site-selectivity and functional group compatibility. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Generally, a range of penchinone A derivatives potently inhibited NO, TNF-α, and IL-6 productions, compared to dexamethasone as a positive control. Notably, penchinone A (8g) and its derivatives (8e and 8f) were found to exhibit anti-inflammatory activity stronger than that of dexamethasone.
Keyphrases
- lps induced
- structure activity relationship
- inflammatory response
- rheumatoid arthritis
- nitric oxide
- molecular docking
- anti inflammatory
- low dose
- high dose
- induced apoptosis
- toll like receptor
- hydrogen peroxide
- gold nanoparticles
- cell proliferation
- nitric oxide synthase
- immune response
- molecularly imprinted
- high resolution
- tandem mass spectrometry