Developing Neolignans as Proangiogenic Agents: Stereoselective Total Syntheses and Preliminary Biological Evaluations of the Four Guaiacylglycerol 8-<i>O</i>-4′-Coniferyl Ethers

Buckler, Joshua N.; Banwell, Martin G.; Kordbacheh, Farzaneh; Parish, Christopher R.; Santiago, Fernando S.; Khachigian, Levon M.

doi:10.1021/acsomega.7b01459

Cited by 7 publications

(3 citation statements)

References 60 publications

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“…In a parallel study the four stereoisomers of GGCE were synthesised and a paper describing the synthesis of these four compounds was recently published [ 57 ]. It was found that all four stereoisomers could enhance endothelial cell tube formation, but e GGCE was the least active.…”

Section: Discussionmentioning

confidence: 99%

Promotion of mammalian angiogenesis by neolignans derived from soybean extracellular fluids

et al. 2018

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Excessive or insufficient angiogenesis is associated with major classes of chronic disease. Although less studied, small molecules which can promote angiogenesis are being sought as potential therapeutics for cardiovascular and peripheral arterial disease and stroke. Here we describe a bioassay-directed discovery approach utilising size exclusion and liquid chromatography to purify components of soybean xylem sap that have pro-angiogenic activity. Using high resolution accurate mass spectrometry and nuclear magnetic resonance spectroscopy, the structure of two pro-angiogenic molecules (FK1 and FK2) were identified as erythro-guaiacylglycerol-8-O-4'-(coniferyl alcohol) ether (eGGCE), and threo-guaiacylglycerol-8-O-4'-(coniferyl alcohol) ether (tGGCE). These two molecules, which are coniferyl neolignan stereoisomers, promoted in vitro angiogenesis in the μM to nM range. Independently sourced samples of eGGCE and tGGCE exhibited comparable pro-angiogenic activity to the soybean derived molecules. The cellular mode of action of these molecules was investigated by studying their effect on endothelial cell proliferation, migration, tube formation and adhesion to the extracellular matrix (ECM) components, fibronectin and vitronectin. They were found to enhance endothelial cell proliferation and endothelial cell tube formation on Matrigel, but did not affect endothelial cell migration or adhesion to fibronectin and vitronectin. Thus, this study has identified two coniferyl neolignan stereoisomers, eGGCE and tGGCE, as pro-angiogenic molecules, with eGGCE being less active than tGGCE.

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Section: Discussionmentioning

confidence: 99%

Promotion of mammalian angiogenesis by neolignans derived from soybean extracellular fluids

et al. 2018

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“…O solvente foi removido sob pressão reduzida, o resíduo foi diluído com água e adicionado ao funil de separação e o produto foi extraído com acetato de etila (3 x 50 mL). A camada aquosa foi então resfriada a 0ºC, acidificado a pH 2-3 com uma solução de HCl 2N, levando a um sólido branco que foi filtrado e seco segundo a metodologia descrita por Buckler et al (2017) [35].…”

Section: áCido 2-(4-alil-2-metoxifenoxi)acético (5)unclassified

“…A validação dos parâmetros utilizados no docking molecular foi realizada através do estudo de re-docking realizado com o ligante co-cristalizado da enzima em questão, o posaconazol, sendo considerados efetivos os parâmetros capazes de reproduzir satisfatoriamente (expressar valores de Root Mean Standard Deviation -RMSD ≤ 2 Å) a conformação desse ligante constante no complexo obtido por cristalografia. [35]. No entanto, a literatura não descreve a síntese do composto 6.…”

Section: Modelagem Molecularunclassified

Síntese, atividade antifúngica e docking molecular de derivados do eugenol

et al. 2020

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Este trabalho descreve a síntese e atividade antifúngica de derivados do eugenol e o docking molecular do eugenol contendo uma unidade 1,2,3-triazólica. Os derivados de eugenol foram obtidos por modificações fenólicas na hidroxila, enquanto a concentração inibitória mínima foi determinada pelo método de microdiluição em caldo. O docking molecular do derivado de eugenol com funcionalidade 1,2,3-triazol foi realizado com a enzima esterol 14-alfa desmetilase (CYP51) e demonstrou que este composto não interage favoravelmente com esta enzima, diferentemente do posaconazol. Os derivados do eugenol foram obtidos com bons rendimentos e a avaliação antifúngica mostrou que, após modificações, a atividade antifúngica foi mantida em alguns exemplos. O resultado do docking molecular nos permitiu vislumbrar alguns motivos que justificam a ausência de atividade antifúngica do derivado de eugenol com funcionalidade 1,2,3-triazol. Em resumo, o artigo fornece informações importantes que ajudarão na realização de pesquisas futuras envolvendo este produto natural.

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Exploiting Nature's Most Abundant Polymers: Developing New Pathways for the Conversion of Cellulose, Hemicellulose, Lignin and Chitin into Platform Molecules (and Beyond)

Banwell

Pollard

Liu

et al. 2021

Chemistry An Asian Journal

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The four most prominent forms of biomass are cellulose, hemicellulose, lignin and chitin. In efforts to develop sustainable sources of platform molecules there has been an increasing focus on examining how these biopolymers could be exploited as feedstocks that support the chemical supply chain, including in the production of fine chemicals. Many different approaches are possible and some of the ones being developed in the authors’ laboratories are emphasised.

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Developing Neolignans as Proangiogenic Agents: Stereoselective Total Syntheses and Preliminary Biological Evaluations of the Four Guaiacylglycerol 8-O-4′-Coniferyl Ethers

Cited by 7 publications

References 60 publications

Promotion of mammalian angiogenesis by neolignans derived from soybean extracellular fluids

Promotion of mammalian angiogenesis by neolignans derived from soybean extracellular fluids

Síntese, atividade antifúngica e docking molecular de derivados do eugenol

Exploiting Nature's Most Abundant Polymers: Developing New Pathways for the Conversion of Cellulose, Hemicellulose, Lignin and Chitin into Platform Molecules (and Beyond)

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