The main theme of our research is the application of synthetic and bioorganic chemistry to problems of biochemical and medicinal relevance. All of the techniques of contemporary organic chemistry, spectroscopy, and chromatography are utilized in a highly interactive, multi-disciplinary environment supported by state-of-the-art instrumentation. Several projects involve collaborations with laboratories specializing in pharmacology, physiology, internal medicine, nephrology, and oncology at UT Southwestern and other institutions.
Natural Products Total Syntheses
In collaboration with a variety of prominent biological laboratories, we are also pursuing the isolation and structure identification of novel natural products with useful pharmacological properties for the treatment of cancer, infectious disease, and other conditions.
Isolated from extracts of the green alga Avrainvillea nigrans and reported in 2007, Nigricanosides A and B are the first examples of a new class of ether-linked glycoglycerolipids. Their relative and absolute configurations are unknown. They arrest human breast cancer MCF-7 cells in mitosis with an IC50 of 3 nM and likely have a unique site and/or mechanism of action. Arrested cells have highly disorganized microtubule spindles, compared with the bipolar spindles of untreated metaphase cells. At 20 ?M, the dimethyl ester stimulates the polymerization of pure tubulin in vitro and inhibits the proliferation of both MCF-7 and human colon cancer HCT-116 cells with an IC50 ? 3 nM.