Identification and structural determination of cancer chemoprevention agents from a marine streptomyces sp

CHED 584

Michelle D. Leibrand, michelle.leibrand@gmail.com, Department of Chemistry, University of San Diego, 5998 Alcala Park, San Diego, CA 92110, John B. MacMillan, jmacmill@ucsd.edu, Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9038, and William Fenical, wfenical@ucsd.edu, Center for Marine Biotechnology and Biomedicine, Univ Calif San Diego, Scripps Institution of Oceanography, La Jolla, CA 92093-0204.
An important avenue for drug discovery is natural products chemistry: the identification and characterization of microbial metabolites. Despite successes in the development of pharmaceuticals from terrestrial microbes, obligate marine bacteria have only recently been identified as a phylogenetically distinct resource. This suggests that the oceans are a promising source of biologically active natural products. The Fenical Lab at the Scripps Institution of Oceanography has screened more than 500 microbial extracts over the past year against a series of cancer chemoprevention assays. In this screening process, actinomycete strain CNS-177, Streptomyces sp. showed activity against NF-κB and aromatase. NF-κB is involved in inflammation and the promotion stage of carcinogenesis, while aromatase is a cytochrome P450-dependent enzyme essential to estrogen biosynthesis. The structures of three active metabolites were solved using UV, MS, and 2D NMR experiments. Stereochemistry was determined by crystallography of derivatives.