DEVELOPMENT OF NOVEL ANTI-CANCER AGENTS BASED ON FUSAROCHROMANONE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的主要目的是开发基于镰刀菌色满酮（FC 101 a）的新型抗癌药物，FC 101 a是一种天然真菌毒素和由木贼镰刀菌产生的真菌代谢产物。FC 101 a由于其多种生物学特性，包括有效的抗血管生成和直接抗肿瘤活性，已被确定为有吸引力的先导候选药物。与大多数其他生物活性天然化合物一样，FC 101 a的效力在体内会受到影响，该项目的目标是在FC 101 a的一些更有效的类似物之间建立结构-功能关系。Elahe Mahdavian博士是该项目的PI，他在合成有机化学和药物化学方面具有专业知识。在LSUS Mahdavian博士的研究实验室中，FC 101 a和几种新型类似物的全合成取得了进展。共有六名LSUS本科生参与了FC 101 a的合成途径。在优化FC 101 a的生物合成方面也取得了进展，从而诱导真菌木贼镰刀菌产生FC 101 a。已经获得了几种木贼镰刀菌菌株，并测试了FC 101 a的存在。我们还从位于孟菲斯的圣裘德癌症中心的新合作者处获得了FC 101 a的真实样品，该样品经过纯化并提交给Clifford博士，用于皮肤癌模型的体外和体内研究。我们还向LSUS的塔拉威廉斯-哈特博士提交了一份样品，以评估FC 101 a在酿酒酵母或芽殖酵母中的生物学功能机制。

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.