Synthesis and PGE2 production inhibition of 1H-furan-2,5-dione and 1H-pyrrole-2,5-dione derivatives

Moon, Jong Taik; Jeon, Ji Young; Park, Hang Ah; Noh, Young-Soo; Lee, Kyung‐Tae; Kim, Jungahn; Choo, Dong Joon; Lee, Jae Yeol

doi:10.1016/j.bmcl.2009.11.067

Cited by 25 publications

(13 citation statements)

References 11 publications

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“…As previously demonstrated (Moon et al ., 2010), we observed that BPD acts as an inhibitor of PGE 2 production through COX‐2 activity. BPD was found to inhibit LPS‐induced PGE 2 production (Figure 1B) and selectively inhibited the COX‐2 activity (IC 50 value = 18.5 µM) with no effect on the COX‐1 activity in a concentration‐dependent manner (Figure 1C).…”

Section: Resultssupporting

confidence: 84%

“…As shown in Figure 1F, LPS significantly enhanced the COX‐2 promoter activity, and BPD inhibited this increase in a concentration‐dependent manner. The inhibitory action of BPD was not due to a cytotoxic effect, because BPD did not affect cell viability, as measured by the MTT assay, at the concentrations (25–100 µM) that suppressed COX‐2 protein and mRNA (Moon et al ., 2010).…”

Section: Resultsmentioning

confidence: 99%

“…Diarylheterocycles and other central ring pharmacophore templates have attracted much attention as potential selective COX‐2 inhibitors. Accordingly, we designed a novel 1H furan‐2,5‐dione derivative, 3‐(benzo[ d ]‐1,3‐dioxol‐5‐yl)‐4‐phenylfuran‐2,5‐dione (BPD), from the vast library of synthetic analogues, and we previously demonstrated that BPD selectively inhibits the production of PGE 2 (Moon et al ., 2010). The chemical structure of BPD is shown in Figure 1A.…”

Section: Introductionmentioning

confidence: 99%

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Potent anti‐inflammatory effect of a novel furan‐2,5‐dione derivative, BPD, mediated by dual suppression of COX‐2 activity and LPS‐induced inflammatory gene expression via NF‐κB inactivation

Shin

Park

Ryu

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSE We previously reported that 3‐(benzo[d]‐1,3‐dioxol‐5‐yl)‐4‐phenylfuran‐2,5‐dione (BPD) showed strong inhibitory effects on PGE2 production. However, the exact mechanism for the anti‐inflammatory effect of BPD is not completely understood. In this study, we investigated the molecular mechanism involved in the effects of BPD on inflammatory mediators in LPS‐stimulated macrophages and animal models of inflammation. EXPERIMENTAL APPROACH The expressions of COX‐2, inducible NOS (iNOS), TNF‐α, IL‐6 and IL‐1β, in LPS‐stimulated RAW 264.7 cells and murine peritoneal macrophages, were determined by Western blot and/or qRT‐PCR, respectively. NF‐κB activation was investigated by EMSA, reporter gene assay and Western blotting. Anti‐inflammatory effects of BPD were evaluated in vivo in carrageenan‐induced paw oedema in rats and LPS‐induced septic shock in mice. KEY RESULTS BPD not only inhibited COX‐2 activity but also reduced the expression of COX‐2. In addition, BPD inhibited the expression of iNOS, TNF‐α, IL‐6 and IL‐1β at the transcriptional level. BPD attenuated LPS‐induced DNA‐binding activity and the transcription activity of NF‐κB; this was associated with a decrease in the phosphorylation level of inhibitory κB‐α (IκB‐α) and reduced nuclear translocation of NF‐κB. Furthermore, BPD suppressed the formation of TGF‐β‐activated kinase‐1 (TAK1)/TAK‐binding protein1 (TAB1), which was accompanied by a parallel reduction of phosphorylation of TAK1 and IκB kinase (IKK). Pretreatment with BPD inhibited carrageenan‐induced paw oedema and LPS‐induced septic death. CONCLUSION AND IMPLICATIONS Taken together, our data indicate that BPD is involved in the dual inhibition of COX‐2 activity and TAK1‐NF‐κB pathway, providing a molecular basis for the anti‐inflammatory properties of BPD.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Potent anti‐inflammatory effect of a novel furan‐2,5‐dione derivative, BPD, mediated by dual suppression of COX‐2 activity and LPS‐induced inflammatory gene expression via NF‐κB inactivation

Shin

Park

Ryu

et al. 2012

British J Pharmacology

Self Cite

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“…Several derivatives, including (S and a polar linking group (which attaches the aromatic ring to a lipophilic group in AA). 30 Addition of a second hydrophobic ring, not coplanar with the original aromatic ring, was found to enhance activity, 35 this second heteroaromatic ring or heterocyclic ring was believed to provide the necessary geometry to attach to AA. 81 Taking indomethacin (benzo[b] pyrrole) as an example, it was found that N-benzoyl moiety seems to play an important role for the COX-1 activity of indomethacin.…”

Section: Structure-activity Relationships (Sar)mentioning

confidence: 99%

“…Several derivatives, including (S indomethacin (Indacin ® ), acemetacin (Emflex ® ) and etodolac (Etodine ® ) as indole derivatives, and ketorolac (Ketolac ® ) as a pyrrole derivative. [33][34][35][36] These compounds blocked prostaglandin synthesis by non-selective inhibition of COX-1 and COX-2 (indomethacin, acemetacin, tolmetin and ketorolac) or by selective inhibition of COX-2 (etodolac) (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents

Fatahala

Khedr

Mohamed

2017

ACSi

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A series of fused pyrroles were synthesized and tested for their in vivo anti-inflammatory activity. Among 14 examined derivatives, 5 derivatives (1b-e, g and 5b), showed a promising anti-inflammatory activity equivalent to reference anti-inflammatory drugs (indomethacin and ibuprofen). A molecular docking study was conducted to interpret the biological activities of the tested compounds. The docking results were complementary with the phase of the biological survey and confirmed the biological effects.

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Pd‐Catalyzed Benzylic CH Functionalization

Thorat¹,

Jain²,

Parganiha³

et al. 2022

Handbook of CH-Functionalization

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Palladium‐catalyzed benzylic CH functionalization has enormous application in industry and academia. Conventional methods have limited scope and selectivity toward functionalization attributed to the very high reactivity of benzylic position particularly benzylic anion. This article discusses the current development of palladium‐catalyzed benzylic CH functionalization involving CC, CO, CN, and CF bond formation which not only tame the reactivity of benzylic anion but also enables its reaction with a large variety of substrates. Some of the applications such as construction of biologically, pharmaceutically, and agrochemical relevant organic molecules have been discussed. This article summarizes palladium‐catalyzed benzylic CH functionalization in a comprehensive way.

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Synthesis and PGE2 production inhibition of 1H-furan-2,5-dione and 1H-pyrrole-2,5-dione derivatives

Cited by 25 publications

References 11 publications

Potent anti‐inflammatory effect of a novel furan‐2,5‐dione derivative, BPD, mediated by dual suppression of COX‐2 activity and LPS‐induced inflammatory gene expression via NF‐κB inactivation

Potent anti‐inflammatory effect of a novel furan‐2,5‐dione derivative, BPD, mediated by dual suppression of COX‐2 activity and LPS‐induced inflammatory gene expression via NF‐κB inactivation

Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents

Pd‐Catalyzed Benzylic CH Functionalization

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