DEVELOPMENT OF NOVEL ANTI-CANCER AGENTS BASED ON FUSAROCHROMANONE

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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.