Lorraine M. Deck

Professor Emeritus

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Organic Chemistry

Contact Information

Email:
Phone: 505-277-6655
Office: Clark Hall Room 350

Education

  • B.S. in Chemistry, 1965, Wayne State University
  • Ph.D. in Chemistry, 1990, University of New Mexico

Research

Our research program focuses on the design and synthesis of novel inhibitors of several proteins, including cholesterol esterase, lactate dehydrogenase, NFkB, urokinase and Abeta aggregates. These inhibitors have potential therapeutic use for treating a wide array of ailments such as cardiovascular disease, malaria, stroke, breast cancer and Alzheimer's disease. Our lead structures of these inhibitors are based on natively active natural products, such as gossypol, curcumin, resveratrol, combrestatin and hemigossypol. By exploiting these natural products' many different scaffolds (including isocoumarins, pyrones, highly substituted naphthoic acids, tetralones, unsaturated diarylketones, benzoxazinones and stilbenes) compounds with greater activity and selectivity are created.

For the development of new therapeutics for Alzheimers disease both curcumin and resveratrol have been shown to inhibit aggregation of Abeta. Analogs are synthesized and tested for activity, and the same analogs are also tested for inhibition of the activation of NFkB. We have found that even slight modifications made to the structures of the analogs results in different biological properties, providing great control in tailoring the subsequent activity profiles.

The synthesis of appropriately substituted isocoumarins and pyrones affords selective inhibitors of the serine proteases, urokinase and cholesterol esterase. Inhibition of pancreatic cholesterol esterase should reduce the incidence of atherosclerotic heart disease. The synthesis of highly substituted naphthoic acids and tetralones provides compounds that bind to the active site of lactate dehydrogenase from both humans and malarial parasites. Inhibitors of human lactate dehydrogenases have potential as therapeutics for stroke victims whereas inhibitors of malarial parasite lactate dehydrogenases have potential as antimalarials.

Selected Publications

  1. W.M. Weber; L.A. Hunsaker; C.N. Roybal; E.V. Bobrovnikova-Marjon; S.F. Abcouwer; R.E. Royer; L.M. Deck; D.L. Vander Jagt. Activation of NFkB is Inhibited by Curcumin and Related Enones Bioorg. Med. Chem. 2006, 14, 2450-2461.
  2. W.M. Weber; L.A. Hunsaker; A.M. Gonzales; J.J. Heynekamp; R.A. Orlando; L.M. Deck; D.L. Vander Jagt. TPA-induced Up-regulation of Activator Protein-1 can be Inhibited or Enhanced by Analogs of the Natural Product Curcumin Biochem. Pharmacol. 2006, 72, 928-940.
  3. J.J. Heynekamp; W.M. Weber; L.A. Hunsaker; A.M. Gonzales; R.A. Orlando; L.M. Deck; D.L. Vander Jagt. Substituted trans-Stilbenes, Including Analogs of the Natural Product Resveratrol, Inhibit the Tumor Necrosis Factor--induced Activation of Nuclear Factor-B J. Med. Chem., 2006, 49, 7182-7189.
  4. S. Pailloux; I. Binyamin; S. Kim; L.M. Deck; B.M. Rapko; B.P. Hay; E.N. Duesler; L. Zakharov; S. Kassel; A.L. Rheingold; R.T. Paine. Oxidation reactivity channels for 2-(pyridin-2-yl)-N,N-diphenylacetamides J. Org. Chem. 2007, 72, 9195-9202.
  5. J.J. Heynekamp; L.A. Hunsaker; T.A. Vander Jagt; R.E. Royer; L.M. Deck; D.L. Vander Jagt. Isocoumarin-based Inhibitors of Pancreatic Cholesterol Esterase Bioorg. Med. Chem. 2008, 16, 5285-5294