Bradley S. Davidson
B.S., 1984, Montana State University
M.S., 1986, Cornell University
Ph.D., 1989, Cornell University
Postdoctoral, 1990, University of Utah
The goal of our research is to study the structural chemistry of naturally occurring compounds, and to understand how structure affects stability, reactivity, and biological activity. This approach has required a merging of experimental and theoretical tools typically applied to three areas of organic chemistry, i.e., organic synthesis, natural products chemistry, and medicinal chemistry. Our research projects often involve a combination of 1) the isolation of new organic entities, 2) the use of both spectral and chemical methods for elucidation of planar and three-dimensional structures, and 3) organic synthesis to support proposed structural assignments and for the preparation of additional compound and analogs for biological evaluation and structure activity relationship studies. Assessment of a molecule’s potential as a chemotherapeutic agent is undertaken in collaboration with pharmacologists.
Within this context, our current studies have been focused in two areas: 1) the discovery of new biologically active naturally natural products, and 2) the synthesis of biologically active natural products and their structural analogs. While many of our efforts have focused on the discovery of new compounds with potentially useful biological activities from either marine organisms, we have recently initiated a collaboration with scientists from Cameroon to investigate plant natural products with potential to treat malaria. Although still in its infancy, the collaborative effort has yielded some biologically active compounds and extracts that are currently under investigation.
Our synthetic efforts have been driven by a need to confirm a proposed chemical structure, generate additional material to undertake or continue biological testing, or to produce structural analogs for structure-activity-relationship (SAR) studies. Past synthetic targets include the DNA-damaging pentathiepin varacin, and beta-carboline natural products didemnolines A-H, and Taxol-like microtubule stabilizing agents laulimalide and isolaulimalide. Our current efforts involve the derivatization of Hedgehog (Hh) pathway inhibitor cyclopamine. The Hh signaling pathway serves as an important regulator of embryonic development, and its misregulation can lead to a variety of cancers, including basel-cell carcinoma, medulloblastoma, small-cell lung cancer, pancreatic adenocarcinoma, and some prostate cancers. Importantly, cyclopamine has been shown to be a potential treatment for Hh pathway-dependent cancers. Our goal is to produce cyclopamine derivatives and conjugates that have improved drug delivery properties.
Selected Recent Publications
Susan L. Mooberry, Georgia Tien, Anne H. Hernandez, Anuchit Plubrukarn, and Bradley S. Davidson, “Laulimalide and Isolaulimalide, New Paclitaxel-like Microtubule-Stabilizing Agents,” Cancer Research 1999, 59, 653-660.
B. Travis Messenger and Bradley S. Davidson, "Synthetic Studies Toward the Microtubule-Stabilizing Agent Laulimalide: Synthesis of the C15-C28 Fragment," Tetrahedron Letters 2001, 42, 801-803.
Geoffry T. Nadolski and Bradley S. Davidson, "Synthetic Studies Toward the Microtubule-Stabilizing Agent Laulimalide: Synthesis of the C1-C14 Fragment," Tetrahedron Letters 2001, 42, 797-800.
Susan L. Mooberry and Bradley S. Davidson, “Laulimalide Microtubule Stabilizing Agents,” 2001, United States Patent Number 6,414,015.
A. Sivaramakrishnan, Geoffry T. Nadolski, Ian A. McAlexander, and Bradley S. Davidson, “An Improved Synthesis of the C15-C28 Fragment of Laulimalide,” Tetrahedron Letters 2002, 43, 213-216.
Robert W. Schumacher, S. C. Talmage, S. A. Miller, K. E. Sarris, Bradley S. Davidson, and Arthur Goldberg, “Isolation and Structure Determination of an Antimicrobial Ester from a Marine Sediment-Derived Bacterium,” Journal of Natural Products 2003, 66, 1291-1293.
Erin A. Clark, Bradley S. Davidson, Paul A. Wender, and Susan L. Mooberry “Laulimalide and Synthetic Laulimalide Analogs are Synergistic with Paclitaxel and 2-Methoxyestradiol,” Molecular Pharmacology 2006, 3, 457-467.