UK-1 is a structurally unique bacterial natural product that was first isolated and characterized in the early 1990s. It was shown to exhibit broad spectrum anticancer activity, which may be a result of its ability to inhibit human topoisomerase II. UK-1 contains convergent Lewis-basic groups which allows it to bind divalent metal ions such as Zn2+. The syntheses of truncated analogs allowed for identification of a minimal pharmacophore necessary for topoisomerase inhibition and suggested a potential role for metal binding. Subsequent analogs of UK-1 have been prepared which are submicromolar inhibitors of replication of hepatitis C virus, influenza H1N1, Zika virus, and the bacterial metallo-b-lactamase NDM-1, an enzyme responsible for bacterial antibiotic resistance. A brief history of their design and synthesis, as well as the preliminary biological results will be discussed.
Paul Smith, Bio
Throughout his research life, Dr. Smith’s focus has been in the area of bioorganic chemistry. As an undergraduate at SUNY Brockport, he worked with Professor Martha Vestling on the biotransformation of polycyclic aromatic hydrocarbons by aquatic plants prevalent in Lake Ontario; he also spent a summer in an REU Program at Roswell Park Memorial Cancer Institute in Buffalo, New York, where he worked with Professor Charles Morreal on the synthesis of DNA intercalating agents as potential cancer drugs. Dr. Smith did his Ph.D. research with Professor Craig Wilcox at the University of Pittsburgh, where he investigated the role of ionic interactions in enzymatic catalysis. In his post-doctoral research with Professors Craig Townsend and Tom Tullius at Johns Hopkins University, he investigated the role of DNA structure on the reactivity of the DNA-cleaving enediyne natural product calicheamicin. Since joining the faculty in the Department of Chemistry and Biochemistry at UMBC, Dr. Smith’s lab has prepared and evaluated cyclodextrin-based enzyme mimics, and designed and synthesized metal-binding small molecules as anti-viral and anti-bacterial agents. Dr. Smith teaches undergraduate organic chemistry and the associated labs as well as advanced courses in spectroscopy for organic chemists and advanced organic reaction mechanisms.
