Structurally complex natural products from diverse biological organisms continue to be a critical source of new chemical entities that serve as lead compounds for drug development and as molecular research probes. Chemical diversity directly correlates with biological diversity, and thus phylogenetically unique organisms from unusual ecosystems are rational sources of novel chemotypes with important biological activities. Taking advantage of recent advances in a range of analytical techniques, with an emphasis on nuclear magnetic resonance (NMR) spectroscopy, our laboratory focuses on the discovery and characterization of natural products relevant to cancer and infectious disease research. Three main projects are: • Biologically active natural products from deep-sea vent organisms. Hydrothermal vents are among the most dynamic and extreme environments on Earth, and many vents exhibit a unique range of habitat diversity and a high degree of endemism. The majority of vent invertebrates acquire fixed carbon and nitrogen from microbial symbionts and free-living microorganisms also form extensive microbial mats on chimney spires and within hydrothermal sediments. Bacterial diversity at deep-sea vents spans most of the currently defined lineages, including the Actinobacteria. This is significant since terrestrial actinomycetes are the source of more than 60% of clinical antibiotics and numerous anticancer agents. • South African tunicates as a source of new anticancer agents and anti-infectives. The East Cape coast of South Africa, where the Indian and Atlantic Oceans mix, exhibits an unprecedented abundance, diversity and high degree of endemism of tunicates. In collaboration with South African scientists, extracts from previously undescribed species of tunicates are being investigated using toxicity to bacteria or human cancer cells to guide rapid, microscale identification of the active components. • Synthesis, mechanism of action and in vivo efficacy of the Panamanian cyanobacterial metabolite coibamide A. This anticancer lead compound and analog structures will be tested for in vivo efficacy once we have a reliable synthetic source of the compounds. The synthesis of coibamide compounds is part of a collaboration with Dr. Phil Proteau (Pharmaceutical Sciences). Furthermore, we are investigating the effect of coibamide A on aggressive, highly metastatic brain tumors through a collaboration with Dr. Jane Ishmael (Pharmaceutical Sciences). Other Panamanian cyanobacteria from terrestrial/freshwater environments are also being investigated for similar compounds. The McPhail laboratory also collaborates with the Department of Botany and Plant Pathology and the USDA Agricultural Research Service on a project to develop a new class of naturally-occurring herbicides for the control of grassy weeds.
College of PharmacyOregon State UniversityCorvallis, OR 97331Phone: 541.737.3424Fax: 541.737.3999