DEVELOPMENT OF NOVEL ANTI-CANCER AGENTS BASED ON FUSAROCHROMANONE

基于镰刀菌酮的新型抗癌药物的开发

• 批准号: 8168140
• 负责人: ELAHE MAHDAVIAN
• 金额: $ 5.55万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168140
• 关键词: Anabolism; Antineoplastic Agents; Biological; Biological Process; Cancer Center; Computer Retrieval of Information on Scientific Projects Database; Development; Funding; Fusarium; Goals; Grant; In Vitro; Institution; Laboratory Research; Lead; Modeling; Mycotoxins; Organic Chemistry; Pathway interactions; Pharmaceutical Chemistry; Property; Research; Research Personnel; Resources; Saccharomyces cerevisiae; Saccharomycetales; Saint Jude Children' s Research Hospital; Sampling; Skin Cancer; Source; Structure-Activity Relationship; Students; Testing; United States National Institutes of Health; analog; base; drug candidate; fungus; fusarochromanone; in vivo; novel; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary goal of this research is to develop novel anti-cancer agents based on fusarochromanone (FC101a), a natural mycotoxin and a fungal metabolite produced by Fusarium equiseti. FC101a has been identified as an attractive lead drug candidate because of its diverse biological properties, including potent anti-angiogenic and direct anti-tumor activity. Like most other bioactive natural compounds, the potency of FC101a is compromised in-vivo, and the project's goal involves the establishment of structure-function relationships among some of FC101a's more potent analogs. The PI of this project, Dr. Elahe Mahdavian has expertise in synthetic organic chemistry and medicinal chemistry. Progress has been made towards the total synthesis of FC101a and several novel analogs in Dr. Mahdavian's research laboratory at LSUS. A total of six undergraduate LSUS students have been involved in the synthetic pathway of FC101a. Progress has also been made in optimizing the biosynthesis of FC101a, whereby the fungus, Fusarium equiseti, is induced to produce FC101a. Several strains of Fusarium equiseti have been obtained and tested for the presence of FC101a. We have also obtained an authentic sample of FC101a from a new collaborator at the St. Jude Cancer Center in Memphis, which was purified and submitted to Dr. Clifford, for in-vitro and in-vivo studies on models of skin cancer. We have also submitted a sample to Dr. Tara Williams-Hart at LSUS for the assessment of the mechanism of FC101a's biological function in Saccharomyces cerevisiae or budding yeast.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的主要目的是基于赤霉菌产生的天然真菌毒素和真菌代谢物赤霉素酮(FC101a)开发新型抗癌药物。FC101a因其多种生物学特性，包括强大的抗血管生成活性和直接抗肿瘤活性，已被确定为有吸引力的先导候选药物。像大多数其他具有生物活性的天然化合物一样，FC101a的效力在体内受到了影响，该项目的目标包括在一些更有效的类似物之间建立结构-功能关系。该项目的PI Elahe Mahdavie博士在合成有机化学和药物化学方面拥有专业知识。马赫达维亚博士在路易斯安那州立大学的研究实验室在FC101a和几种新型类似物的全合成方面取得了进展。共有六名路易斯安那州立大学的本科生参与了FC101a的合成途径。在优化FC101a的生物合成方面也取得了进展，通过诱导赤霉菌产生FC101a。已经获得了几个木质镰刀菌菌株，并对其进行了FC101a的检测。我们还从孟菲斯圣裘德癌症中心的一位新合作者那里获得了一份真正的FC101a样本，该样本被提纯并提交给Clifford博士，用于皮肤癌模型的体外和体内研究。我们还向路易斯安那州立大学的塔拉·威廉姆斯-哈特博士提交了一个样本，用于评估FC101a在酿酒酵母或萌芽酵母中的生物功能机制。