The RTI-NPP group has been involved for 35 years in a search for natural products with anti- cancer activity based on the philosophy that secondary metabolites of plant, murine, or fungal origin may have valuable anti- cancer activity. Early studies resulted in isolation of camptothecin and taxol now in extensive clinical use, directly or as analogs, in anti-cancer chemotherapy. RTI wishes to continue this long-term effort as part of a consortium response to an NCI National Cooperative Natural Product rug Discovery Groups (NCNPDDG) Grant Application involving the University of Illinois at Chicago (UIC), Bristol-Myers Squib (BMS), and the Research Triangle Institute (RTI). RTI will receive samples of crude extracts from UIC process them for consolidation into 96-well mother plates. Daughter plates will be prepared and shipped to BMS for inclusion in their anti-cancer test battery. Active extracts will undergo bioassay- guided fractionation at RTI suing the same BMS assay(s) that identified the activity. The structure of pure compounds will be obtained utilizing all modern methods including UV, IRF, MS, LC-MS, NMR, and X-Ray.. When large quantities of active plants are collected and assigned to RTI, quantities of plant sample up to 10-20 kg will be extracted and fractionated. Pure samples thus obtained will be supplied as requested by the Principal Investigator for in vivo evaluations at RTI (Topo I and Topo II inhibition), UIC or BMS. In this manner RTI and its consortium partners, UIC and BMS hype to make a major contribution to cancer chemotherapy. The functional bioassays used at RTI to fractionate active crude extracts will be essentially those currently used in Oncology Drug Discovery at BMS. These include, but are not limited to, cell cycle and signal transduction targets known to be involved in cancer growth and inhibitors of angiogenesis. RTI has the facilities to establish these assays and provide the sample throughput necessary to conduct the timely bioassay- guided fractionation of the crude extracts. Pure compounds will also be evaluated for their ability to inhibit topoisomerase I.
Showing the most recent 10 out of 84 publications
