Design of PPAR-γ agonist based on algal metabolites and the endogenous ligand 15-deoxy-Δ12, 14-prostaglandin J2

Zhang, Ju; Hong, Jongki; Ullah, Sultan; Kim, Eun La; Zhao, Chang-Hao; Kim, Suhkmann; Jung, Jee H.

doi:10.1016/j.ejmech.2018.08.090

Cited by 8 publications

(6 citation statements)

References 32 publications

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“…Generally, after ligand binding, the activated PPAR-γ will translocate to the nucleus and bind to NF-κB to repress the gene expression of proinflammatory mediators. In our previous study, the PPAR-γ agonistic activity of (+)-( R , E )- 6a1 was evaluated by luciferase assay by using the PPRE-luciferase reporter plasmid [18]. Herein, we used Western blot to assess the protein level of the translocated PPAR-γ at the nucleus due to activation by (+)-( R , E )- 6a1 in RAW264.7 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Compound (+)-( R , E )- 6a1 was synthesized by our group [18]. Dimethylsulfoxide (DMSO), dexamethasone (DEX), lipopolysaccharide (LPS), Griess reagent were purchased from Sigma-Aldrich (St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Thereafter, by incorporating the key structural motifs of these natural products, we synthesized a new class of endocyclic enone jasmonate derivatives as anti-inflammatory leads [16,17]. In a further study, we synthesized an exocyclic enone jasmonate derivative, (+)-( R , E )- 6a1 , as a potent PPAR-γ agonist that share the key exocyclic enone moiety with the endogenous PPAR-γ ligand, 15d-PGJ 2 [18] (See Supplementary Materials). Typical PPAR-γ ligands, such as rosiglitazone and 15d-PGJ 2 , are composed of three distinct partial structures, a polar head, linker, and a hydrophobic tail (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…The exocyclic α,β -unsaturated ketone (enone) moiety of 15d-PGJ 2 was reported to be essential for covalent bonding with Cys 285 in the PPAR-γ LBD. Similar to 15d-PGJ 2 , the enone functionality of (+)-( R , E )- 6a1 may contribute to covalent bonding to the PPAR-γ LBD, and this additional covalent bonding may contribute to the activation of PPAR-γ [18,19,20]. In a continuing study, we investigated the in vitro anti-inflammatory effects of the PPAR-γ agonist, (+)-( R , E )- 6a1, in RAW264.7 murine macrophages.…”

Section: Introductionmentioning

confidence: 99%

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An Algal Metabolite-Based PPAR-γ Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-κB Pathway

Zhang

Hong

et al. 2019

Marine Drugs

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In our previous study, a synthetic compound, (+)-(R,E)-6a1, that incorporated the key structures of anti-inflammatory algal metabolites and the endogenous peroxisome proliferator-activated receptor γ (PPAR-γ) ligand 15-deoxy-∆12,14-prostaglandin J2 (15d-PGJ2), exerted significant PPAR-γ transcriptional activity. Because PPAR-γ expressed in macrophages has been postulated as a negative regulator of inflammation, this study was designed to investigate the anti-inflammatory effect of the PPAR-γ agonist, (+)-(R,E)-6a1. Compound (+)-(R,E)-6a1 displayed in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages. Compound (+)-(R,E)-6a1 suppressed the expression of proinflammatory factors, such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), possibly by the inhibition of the nuclear factor-κB (NF-κB) pathway. In macrophages, (+)-(R,E)-6a1 suppressed LPS-induced phosphorylation of NF-κB, inhibitor of NF-κB α (IκBα), and IκB kinase (IKK). These results indicated that PPAR-γ agonist, (+)-(R,E)-6a1, exerts anti-inflammatory activity via inhibition of the NF-κB pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An Algal Metabolite-Based PPAR-γ Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-κB Pathway

Zhang

Hong

et al. 2019

Marine Drugs

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“…α-Substituted enones serve as important scaffolds in biologically active compounds and natural products . They are also valuable synthetic building blocks in synthetic organic chemistry because of their versatile reactivity .…”

mentioning

confidence: 99%

Stereoselective Fluoroalkylacylation of Alkynes via Cooperative N-Heterocyclic Carbene/Palladium Catalysis

Huang,

Wang,

Zhang

et al. 2024

Org. Lett.

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Herein, a cooperative N-heterocyclic carbene- and palladium-catalyzed three-component reaction of alkynes with aldehydes and fluoroalkyl iodides is developed. A series of biologically valuable CF 2 R-incorporated α-substituted enones was obtained in moderate to good yields. This mild catalytic method exhibits exclusive regio- and stereoselectivity, excellent functional group tolerance, and a broad substrate scope including terminal and internal alkynes. Mechanistic investigations disclose that this alkyne fluoroalkylacylation proceeds via a radical relay process in which vinyl iodides serve as putative reaction intermediates.

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Molecular Cloning and Transient Expression of Recombinant Human PPARγ in HEK293T Cells Under an Inducible Tet-on System

et al. 2019

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Design of PPAR-γ agonist based on algal metabolites and the endogenous ligand 15-deoxy-Δ12, 14-prostaglandin J2

Cited by 8 publications

References 32 publications

An Algal Metabolite-Based PPAR-γ Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-κB Pathway

An Algal Metabolite-Based PPAR-γ Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-κB Pathway

Stereoselective Fluoroalkylacylation of Alkynes via Cooperative N-Heterocyclic Carbene/Palladium Catalysis

Molecular Cloning and Transient Expression of Recombinant Human PPARγ in HEK293T Cells Under an Inducible Tet-on System

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