Synthesis and Evaluation of Anti-Tumor Flavanoids
抗肿瘤黄酮类化合物的合成及评价
基本信息
- 批准号:8318455
- 负责人:
- 金额:$ 2.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-09-29 至 2012-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAlkylationBindingBinding SitesBiologicalBiological FactorsCancer CenterCancer EtiologyCancer cell lineCatalysisCell AdhesionCellsCessation of lifeChemicalsCollaborationsDU145DataDrug KineticsElectrostaticsEvaluationExhibitsFlavanonesFutureGenisteinGenomicsGoalsGrantGrowthHealthHumanHydrogen BondingHydroxylationInstitutesInvestigationIsoflavonesKnowledgeLNCaPLaboratoriesLibrariesMalignant neoplasm of prostateMetalloproteasesMetastatic Prostate CancerMethodologyMethodsMilk ThistleMilk thistle extractModelingNeoplasm MetastasisPC3 cell linePatternPhosphotransferasesPositioning AttributeProcessPropertyProstateReportingResearchRouteScreening procedureSophoraTestingTherapeuticThioureaUnited StatesUnited States National Institutes of HealthUniversitiesanalogbasecancer cellcell motilitychemotherapydesignenantiomerflavanoidflavanoneimprovedinterestisoflavanoneisosilybinmalemalignant breast neoplasmmedical schoolsprogramssoytumor
项目摘要
DESCRIPTION (provided by applicant): The overall goal of this research is to develop and utilize asymmetric catalysis to synthesize anti-prostate cancer (PCa) flavanoids. PCa is the second most common cause of cancer death in US males, death with is usually caused by metastasis. New therapies to treat PCa will have a direct and beneficial impact on the health of the United States.
Genistein, the principal isoflavone in soy, inhibits the initiating steps of cell detachment and cell invasion of prostate cancer cells as well as metastasis. Recently, we discovered that 2,3-dihydrogenistein maintains anti-invasive activity. This led us to believe that isoflavanones might be a class of compounds that is effective against PCa metastasis. The long-term goals of my research are to 1) develop and utilize asymmetric catalysis to synthesize enantioenriched isoflavanones that maintain anti-invasive activity but lack growth inhibitory activity and 2) synthesize and evaluate the flavanone natural products kurarinone isosilybin B. Our central hypothesis is that optically active flavanoids are underdeveloped molecules for the treatment of PCa and stereoselective methods to access these compounds will have a dramatic impact on the future of chemotherapy. The specific aims of my research during the proposed grant period are:
Specific Aim 1: Develop new catalytic asymmetric methods to access antimetastatic enantioenriched C3 substituted isoflavanones. Utilizing the binding site model for genistein that was recently developed by Scheldt and Bergan, we will be able to design and synthesize more potent and selective isoflavanones.
Specific Aim 2: Synthesize the flavanone natural products kurarinone and isosilybin B. Both flavanones
display anti-PCa activity, yet no enantioselective syntheses of these molecules has been reported.
In order to discover the biological targets of our compounds and accordingly modify them, we have
established a collaboration with Dr. Raymond Bergan, the Director of Experimental Therapeutics for the
Robert H. Lurie Cancer Center at the Feinberg School of Medicine at Northwestern University. He directs a laboratory based research program focusing on the pharmacologic manipulation of PCa cell motility. He will evaluate our compounds for their antimetastatic efficacy and we will use the findings of his testing to synthesize more selective and potent isoflavanoids and optimize pharmacokinetic properties.
描述(由申请人提供):本研究的总体目标是开发和利用不对称催化合成抗前列腺癌(PCa)类黄酮。前列腺癌是美国男性癌症死亡的第二大常见原因,通常由转移引起。治疗前列腺癌的新疗法将对美国人的健康产生直接和有益的影响。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A biomimetic strategy to access the silybins: total synthesis of (-)-isosilybin A.
- DOI:10.1021/ol503303w
- 发表时间:2015-01-02
- 期刊:
- 影响因子:5.2
- 作者:McDonald, Benjamin R.;Nibbs, Antoinette E.;Scheidt, Karl A.
- 通讯作者:Scheidt, Karl A.
Catalytic asymmetric alkylation of substituted isoflavanones.
- DOI:10.1021/ol901676f
- 发表时间:2009-09-03
- 期刊:
- 影响因子:5.2
- 作者:Nibbs AE;Baize AL;Herter RM;Scheidt KA
- 通讯作者:Scheidt KA
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Antoinette Evadney Nibbs其他文献
Antoinette Evadney Nibbs的其他文献
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{{ truncateString('Antoinette Evadney Nibbs', 18)}}的其他基金
Synthesis and Evaluation of Anti-Tumor Flavanoids
抗肿瘤黄酮类化合物的合成及评价
- 批准号:
7695570 - 财政年份:2008
- 资助金额:
$ 2.12万 - 项目类别:
Synthesis and Evaluation of Anti-Tumor Flavanoids
抗肿瘤黄酮类化合物的合成及评价
- 批准号:
7616280 - 财政年份:2008
- 资助金额:
$ 2.12万 - 项目类别:
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