A Combined Experimental and Computational Study of Vam3, a Derivative of Resveratrol, and Syk Interaction

Jiang, Ming; Liu, Ren Ping; Chen, Ying; Zheng, Qisheng; Fan, Saijun; Liu, Peixun

doi:10.3390/ijms150917188

Cited by 10 publications

(8 citation statements)

References 30 publications

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“…Furthermore, the data demonstrated that most of the amino acid interactions established by Gleevec could be relevant in providing better chemical stability and lower binding energy in silico, although this ligand is not specific to Syk. In this paper, we also report that all Syk inhibitors interact with Met450, Leu453, and Pro455; these amino acids are of great importance because of their high levels of Syk specificity [ 41 , 42 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

Syk Inhibitors: New Computational Insights into Their Intraerythrocytic Action in Plasmodium falciparum Malaria

Marchetti

Dessì

Dallocchio

et al. 2020

IJMS

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Resistance to antimalarial drugs has spread rapidly over the past few decades. The WHO recommends artemisinin-based combination therapies for the treatment of uncomplicated malaria, but unfortunately these approaches are losing their efficacy in large areas of Southeast Asia. In 2016, artemisinin resistance was confirmed in 5 countries of the Greater Mekong subregion. We focused our study on Syk inhibitors as antimalarial drugs. The Syk protein is present in human erythrocytes, and the membrane of protein band 3 is its major target following activation by oxidant stress. Tyr phosphorylation of band 3 occurs during P. falciparum growth, leading to the release of microparticles containing hemicromes and structural weakening of the host cell membrane, simplifying merozoite reinfection. Syk inhibitors block these events by interacting with the Syk protein’s catalytic site. We performed in vitro proteomics and in silico studies and compared the results. In vitro studies were based on treatment of the parasite’s cellular cultures with different concentrations of Syk inhibitors, while proteomics studies were focused on the Tyr phosphorylation of band 3 by Syk protein with the same concentrations of drugs. In silico studies were based on different molecular modeling approaches in order to analyze and optimize the ligand–protein interactions and obtain the highest efficacy in vitro. In the presence of Syk inhibitors, we observed a marked decrease of band 3 Tyr phosphorylation according to the increase of the drug’s concentration. Our studies could be useful for the structural optimization of these compounds and for the design of novel Syk inhibitors in the future.

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Section: Resultsmentioning

confidence: 99%

Syk Inhibitors: New Computational Insights into Their Intraerythrocytic Action in Plasmodium falciparum Malaria

Marchetti

Dessì

Dallocchio

et al. 2020

IJMS

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“…Spleen tyrosine kinase, also known as Syk, plays crucial roles in both adaptive immune responses and innate immune responses (Yi et al, 2014). Amurensin H has been shown to be an ATP-competitive inhibitor of Syk in vitro (Jiang et al, 2014). Binding of ligand and cell membrane receptors that associate with transmembrane proteins with cytoplasmic domains containing immunoreceptor tyrosine-based activation motifs (ITAMs) leads to the recruitment of Syk.…”

Section: Introductionmentioning

confidence: 99%

Amurensin H, a Derivative From Resveratrol, Ameliorates Lipopolysaccharide/Cigarette Smoke–Induced Airway Inflammation by Blocking the Syk/NF-κB Pathway

et al. 2019

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Amurensin H, a resveratrol dimer derived from Vitis amurensis Rupr, has several biological effects, including anti-inflammatory and antioxidant activities. Studies have found that amurensin H attenuated asthma-like allergic airway inflammation. However, its protective activity on chronic obstructive pulmonary disease (COPD) airway inflammation is not fully explored. The present study used a lipopolysaccharide (LPS)/cigarette smoke–induced mice model and an LPS-stimulated THP-1–derived macrophages model to measure the lung tissue’s morphology changes. The results showed that amurensin H ameliorated the histological inflammatory alterations in the lung tissues, leading to a decrease in the expression of interleukin 6 (IL-6), IL-17A, tumor necrosis factor α (TNF-α), and interferon γ in bronchoalveolar lavage fluid. Amurensin H also significantly inhibited the release of IL-1β, IL-6, IL-8, and TNF-α in LPS-stimulated THP-1–derived macrophages. Furthermore, amurensin H markedly inhibited the expressions of p-Syk, nuclear factor κB (NF-κB), and p-NF-κB both in vivo and in vitro. Results from cotreatment with Syk inhibitor BAY61-3606 and NF-κB inhibitor BAY11-7082 in vitro revealed that amurensin H’s protective effect against airway inflammation could be due partly to the inhibition of the Syk/NF-κB pathway. These findings suggest that amurensin H shows therapeutic effects on COPD airway inflammation, and inhibiting the Syk/NF-κB pathway might be part of its underlying mechanisms.

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“…In this study we describe total syntheses of viniferifuran ( 2 ),11 its isomer anigopreissin A ( 11 )12 and the recently reported resveratrol‐piceatannol hybrid ( 12 )13 (Figure 1). Viniferifuran is a competitive inhibitor of syk kinase (IC 50 =62 nM)14 and this mechanism is believed to be key for the anti‐inflammatory activity of viniferifuran. Anigopreissin A was recently discovered as an inhibitor of HIV‐1 reverse transcriptase (IC 50 =8 μM) including two mutant enzymes resistant to the clinical drug nevirapine 12b.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of Viniferifuran, Resveratrol‐Piceatannol Hybrid, Anigopreissin A and Analogues – Investigation of Demethylation Strategies

Elofsson

2016

Adv Synth Catal

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Resveratrol‐based natural products constitute a valuable source of unique compounds with diverse biological activities. In this report we investigate demethylation strategies to minimize formation of cyclized and dimerized products during the synthesis of viniferifuran and analogues. We found that boron trichloride/tetra‐n‐butylammonium iodide (BCl3/TBAI) is typically more effective than boron tribromide (BBr3). Based on these findings we carried out the first syntheses of dehydro‐δ‐viniferin, resveratrol‐piceatannol hybrid and anigopreissin A. In addition, we have developed a short and efficient route to viniferifuran that was obtained in 13% yield over six steps.

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A Combined Experimental and Computational Study of Vam3, a Derivative of Resveratrol, and Syk Interaction

Cited by 10 publications

References 30 publications

Syk Inhibitors: New Computational Insights into Their Intraerythrocytic Action in Plasmodium falciparum Malaria

Syk Inhibitors: New Computational Insights into Their Intraerythrocytic Action in Plasmodium falciparum Malaria

Amurensin H, a Derivative From Resveratrol, Ameliorates Lipopolysaccharide/Cigarette Smoke–Induced Airway Inflammation by Blocking the Syk/NF-κB Pathway

Total Synthesis of Viniferifuran, Resveratrol‐Piceatannol Hybrid, Anigopreissin A and Analogues – Investigation of Demethylation Strategies

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