Synthesis and activity of N-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)acetamide analogues as anticolitis agents via dual inhibition of TNF-α- and IL-6-induced cell adhesions

Karmacharya, Ujjwala; Regmi, Sushil Chandra; Awasthi, Bhuwan Prasad; Chaudhary, Prakash; Kim, Ye Eun; Lee, Iyn-Hyang; Nam, Tae‐gyu; Kim, Jung-Ae; Jeong, Byeong‐Seon

doi:10.1016/j.bmcl.2021.128059

Cited by 8 publications

(10 citation statements)

References 35 publications

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“…Experimental results showed nitric oxide synthase iNOS and common inflammatory factors (IL-1β, IL-6, TNF-α) play a key role in inflammation development (29,30). Following LPSstimulated macrophages, the expression of iNOS, IL-1β, IL-6, and TNF-α related genes increased significantly.…”

Section: Effect Of Different Rchp-s Concentrations On Cytokine Secretionmentioning

confidence: 98%

Anti-inflammatory Effect of a Novel Pectin Polysaccharide From Rubus chingii Hu on Colitis Mice

Kong

et al. 2022

Front. Nutr.

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Rubus chingii Hu has been used as a functional food for a long time. A novel pectin polysaccharide named RCHP-S from R. chingii Hu was structurally identified and explored its anti-inflammatory effect on colitis mice. RCHP-S was composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose. NMR spectroscopy and methylation analysis showed that RCHP-S was mainly composed of HG-type pectin domains but also contains a small amount of RG-I. The anti-inflammatory tests indicated that the mouse macrophage RAW 264.7 cells pretreated with RCHP-S could show a significant inhibitory effect on the mRNA level of iNOS, IL-1β, IL-6, and TNF-α in vitro. Polysaccharide RCHP-S reduced the enteritis symptoms in dextran sulfate sodium (DSS)-induced colitis mice by inhibiting released inflammatory factors. These results indicated that the R. chingii Hu polysaccharide can be used as food additives for the treatment of intestinal inflammation.

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Section: Effect Of Different Rchp-s Concentrations On Cytokine Secretionmentioning

confidence: 98%

Anti-inflammatory Effect of a Novel Pectin Polysaccharide From Rubus chingii Hu on Colitis Mice

Kong

et al. 2022

Front. Nutr.

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“…In this study, we synthesized 2,4,5-trimethylpyridin-3-ol analogues with enhanced dual inhibitory activity against TNFα and IL-6. As depicted in Scheme , the synthesis of 6 analogues followed a methodology described elsewhere. − In brief, we initiated the synthesis with pyridoxine·HCl ( 1 ) and converted its two benzylic hydroxyl groups to chlorides by treatment with SOCl 2 . These chlorides were then reductively removed to yield 2 .…”

Section: Resultsmentioning

confidence: 99%

G Protein-Coupled Estrogen Receptor-Mediated Anti-Inflammatory and Mucosal Healing Activity of a Trimethylpyridinol Analogue in Inflammatory Bowel Disease

Awasthi,

Chaudhary,

Lim

et al. 2024

J. Med. Chem.

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Inflammatory bowel disease (IBD) is characterized by abnormal immune responses, including elevated proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the gastrointestinal (GI) tract. This study presents the synthesis and anti-inflammatory evaluation of 2,4,5-trimethylpyridin-3ol analogues, which exhibit dual inhibition of TNFα-and IL-6-induced inflammation. Analysis using in silico methods, including 3D shapebased target identification, modeling, and docking, identified G protein-coupled estrogen receptor 1 (GPER) as the molecular target for the most effective analogue, 6-26, which exhibits remarkable efficacy in ameliorating inflammation and restoring colonic mucosal integrity. This was further validated by surface plasmon resonance (SPR) assay results, which showed direct binding to GPER, and by the results showing that GPER knockdown abolished the inhibitory effects of 6-26 on TNFα and IL-6 actions. Notably, 6-26 displayed no cytotoxicity, unlike G1 and G15, a well-known GPER agonist and an antagonist, respectively, which induced necroptosis independently of GPER. These findings suggest that the GPER-selective compound 6-26 holds promise as a therapeutic candidate for IBD.

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“…In other reports, both TNF-a and IL-6 have been investigated as the main molecules of interest. As a proinflammatory cytokine, IL-6 modulates anti-inflammatory mechanisms by targeting NF-κB, thereby inhibiting the cellular production of TNF-α, which could be one of the mechanisms underlying NF-κB suppression that we have observed in an anti-inflammatory state [ 25 ]. In our current study, L. curvatus BYB3 significantly weakened the DSS-induced overexpression of colonic TNF-R1 and IL-6; this effect was likely mediated by the attenuation of activated monocyte and macrophage infiltration (primary sources of these two proteins) [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Latilactobacillus curvatus BYB3 Isolated from Kimchi Alleviates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice by Inhibiting IL-6 and TNF-R1 Production

Wang

Dingyun

Meng

et al. 2022

J. Microbiol. Biotechnol.

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Recent studies have shown that probiotics have health-promoting effects, particularly intestinal immune modulation. In this study, we focused on the immunomodulatory properties of Latilactobacillus curvatus BYB3, formerly called Lactobacillus curvatus, isolated from kimchi. In a mouse model of 14-day dextran sulfate sodium (DSS)-induced colitis, treatment with L. curvatus BYB3 significantly decreased the disease activity index, colon length, and weight loss. Moreover, histological analyses showed that L. curvatus BYB3 protected the structural integrity of the intestinal epithelial layer and mucin-secreting goblet cells from DSS-induced damage, with only slight infiltration by immune cells. To evaluate the molecular mechanisms underlying L. curvatus BYB3-driven inhibition of interleukin 6 production, possible in vivo anti-inflammatory effects of L. curvatus BYB3 were examined in the same mouse model. In addition, significantly lower levels of IL-6 and tumor necrosis factor receptor 1 upregulation were seen in the DSS+BYB3 group (compared to that in the DSS group). These results indicate that L. curvatus BYB3 exhibits health-promoting effects via immune modulation; and therefore, it can be used to treat various inflammatory diseases.

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Synthesis and activity of N-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)acetamide analogues as anticolitis agents via dual inhibition of TNF-α- and IL-6-induced cell adhesions

Cited by 8 publications

References 35 publications

Anti-inflammatory Effect of a Novel Pectin Polysaccharide From Rubus chingii Hu on Colitis Mice

Anti-inflammatory Effect of a Novel Pectin Polysaccharide From Rubus chingii Hu on Colitis Mice

G Protein-Coupled Estrogen Receptor-Mediated Anti-Inflammatory and Mucosal Healing Activity of a Trimethylpyridinol Analogue in Inflammatory Bowel Disease

Latilactobacillus curvatus BYB3 Isolated from Kimchi Alleviates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice by Inhibiting IL-6 and TNF-R1 Production

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