Enabling Elucidation of the Biological Activity of Resveratrol Natural Products with Synthesis
通过合成阐明白藜芦醇天然产物的生物活性
基本信息
- 批准号:9219786
- 负责人:
- 金额:$ 27.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-02-01 至 2020-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsAffinityAgingAnti-Inflammatory AgentsAnti-inflammatoryAntidiabetic DrugsAntioxidantsApoptoticArchitectureBeliefBindingBiologicalBiological ProcessBiological ProductsBiomimeticsCell Culture TechniquesCharacteristicsChemicalsChemistryCollaborationsCollectionCommunitiesComplexConsumptionCouplingDegenerative DisorderDevelopmentDimerizationElectronsEmployee StrikesEpidemiologyEvaluationFree RadicalsGene ExpressionGene Expression RegulationGenomicsHealthHealth BenefitHomeostasisHumanIn VitroIncidenceIndustryInvestigationKineticsLaboratoriesLettersLibrariesLife ExtensionLigandsLipid BilayersLongevityMeasurementMeasuresMethodologyMethodsMolecularMolecular ProbesNatural ProductsOrganic SynthesisOxidation-ReductionOxidative StressPaperPhenolsPhysiologicalPreparationPropertyProteinsReactive Oxygen SpeciesReportingResearchResponse ElementsResveratrolRoleRouteSeriesSignal TransductionSupplementationUniversitiesaqueousbasecellular targetingdimerepidemiology studyexperimental studyfood consumptionhigh throughput screeningindolineinhibitor/antagonistinterestlipid peroxidation inhibitoroxidationperhydroxyl radicalprofessorprophylacticquinone methidered winescreening
项目摘要
PROJECT SUMMARY
The current level of public interest concerning the health benefits of antioxidant supplements is
remarkable and is driven by the belief – on the basis of epidemiological evidence – that the
consumption of foods that are rich in antioxidants is associated with lower incidence of
degenerative disease and corresponding increase in longevity. Resveratrol is a particularly
striking example, and one where its biological activity and its oligomers has been a highly
contentious topic of debate for nearly 20 years. There is significant evidence that resveratrol has
anticancer, antidiabetic, and anti-inflammatory action, as well as life extension properties. The
mechanism of action for a simple molecule such as resveratrol is difficult to elucidate, since it is
a relatively promiscuous ligand that has low binding affinity towards its target proteins. As a
consequence of electron rich phenols, it is tempting to attribute many of these beneficial
properties to its ability to act as an antioxidant. Indeed, this association of antioxidant capacity
and its implications for human health has made radical quenching experiments ubiquitous in the
isolation papers of resveratrol based natural products. Despite extensive research within this
arena, there remains controversy over the benefits of antioxidants and their role in regulating
oxidative stress. In particular, there is a paucity of mechanistic understanding of the mode of
action of antioxidants and their metabolites at a molecular level. Accurate measurements of the
kinetics of ROS (reactive oxygen species) quenching by resveratrol are much more relevant to
understanding the role of resveratrol as an antioxidant and its biological activity. In fact, the
kinetics of this radical trapping by resveratrol suggest that it is highly unlikely that its primary role
is that of an antioxidant in a biological setting. In conjunction with the group of Professor Derek
Pratt (University of Ottawa), we will: (1) Develop cross-coupling methodologies using persistent
radicals for the synthesis of dihydrobenzofuran-containing resveratrol natural products
andbroadly evaluate the biological activity of these compounds; and (2) Determine the kinetics
of peroxyl radical-trapping of the compounds prepared in aim 1 in organic and aqueous solution,
lipid bilayers and cell culture; determine the anti-ferroptotic potential of good inhibitors of lipid
peroxidation and the anti-apoptotic potential of good inhibitors of cytosolic ROS formation;
determine the kinetics, mechanisms and products of resveratrol autoxidation under
physiologically-relevant conditions and extend these studies to resveratrol dimers/oligomers;
determine the electrophilic potential of resveratrol’s oxidative degradation products and carry
out experiments to identify their cellular targets; extend these studies to resveratrol
dimers/oligomers.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Corey Stephenson其他文献
Corey Stephenson的其他文献
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{{ truncateString('Corey Stephenson', 18)}}的其他基金
Free radical strategies for bioactive molecule synthesis-Diversity Supplement
生物活性分子合成的自由基策略-多样性补充
- 批准号:
10671888 - 财政年份:2022
- 资助金额:
$ 27.11万 - 项目类别:
Free radical strategies for bioactive molecule synthesis
生物活性分子合成的自由基策略
- 批准号:
10330824 - 财政年份:2022
- 资助金额:
$ 27.11万 - 项目类别:
Free radical strategies for bioactive molecule synthesis
生物活性分子合成的自由基策略
- 批准号:
10534216 - 财政年份:2022
- 资助金额:
$ 27.11万 - 项目类别:
Free radical strategies for bioactive molecule synthesis - Undergraduate Supplement
生物活性分子合成的自由基策略 - 本科生补充材料
- 批准号:
10809306 - 财政年份:2022
- 资助金额:
$ 27.11万 - 项目类别:
Photoredox Catalysis Applications to Bioactive Compounds
光氧化还原催化在生物活性化合物中的应用
- 批准号:
8601711 - 财政年份:2011
- 资助金额:
$ 27.11万 - 项目类别:
Photoredox Catalysis Applications to Bioactive Compounds
光氧化还原催化在生物活性化合物中的应用
- 批准号:
8750909 - 财政年份:2011
- 资助金额:
$ 27.11万 - 项目类别:
Photoredox Catalysis Applications to Bioactive Compounds
光氧化还原催化在生物活性化合物中的应用
- 批准号:
8027011 - 财政年份:2011
- 资助金额:
$ 27.11万 - 项目类别:
Photoredox Catalysis Applications to Bioactive Compounds
光氧化还原催化在生物活性化合物中的应用
- 批准号:
8206535 - 财政年份:2011
- 资助金额:
$ 27.11万 - 项目类别:
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