Thomas W. Bell

Professor

Organic and Bioorganic Chemistry

B.S. (1974), California Institute of Technology; Ph.D. (1980), University College, University of London (F. Sondheimer); NIH Postdoctoral Fellow (1980-1982), Cornell University (J. Meinwald); Fellow of the American Association for the Advancement of Science (1995-present)

E-mail: twb [at] unr.edu
Phone: 775-784-1842
FAX: 775-784-6804
Office: CB 334

Thomas W. Bell

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Research Interests

The Bell research group uses organic synthesis to make new molecules that are tailored for various purposes. The research projects generally combine molecular and synthetic design, preparation, spectroscopy, and studies of structure and function. The unifying theme of these projects is molecular devices, designed especially to act as drugs interfering with biochemical processes, or to perform as switches, motors, or actuators.

Our major research area is medicinal chemistry. We are especially interested in designing and discovering novel antiviral drugs. For example, we have synthesized a series of drugs, called CADA compounds, which inhibit entry of the HIV virus into host cells. This is accomplished by down-modulating CD4, the cell-surface receptor required for binding of the virus. Current work is aimed at determining the molecular mechanism by which CADA compounds perform this unique task.

A second project aims to synthesize molecular-scale motors and actuators. In collaboration with the Cline research group, we have designed rotary, light-driven molecular motors. In model studies, we have derivatized the dibenzofulvene chromophore to produce an efficient, photon-activated driver for molecular motors that are targets of our current synthetic studies.

Structures of anti-HIV drugs: CADA and unsymmetrical analogs
CADA structure

X-Ray Crystal Structure of CADA (Free Base Form)
CADA

X-Ray structure of Z-NTEF, a molecular motor model compound
NTEF

Selected Publications

Bell, T. W. Improving Potencies and Properties of CD4 Down-Modulating CADA Analogs Expert Opin. Drug Discov. 2011, 7, 39-48.

Ismail, A. I.; Mantha, J. H.; Kim, H. J.; Bell, T. W.; Cline, J. I. Controlling the spatial orientation of molecular actuators: Polarized photoisomerization of 2-Nitro-9-(2,2,2-triphenylethylidene)fluorene in a thin polymer matrix. J. Phys. Chem. A 2011, 115, 419-427.

Demillo, V. G.; Goulinet-Mateo, F.; Kim, J.; Schols, D.; Vermeire, K.; Bell, T. W. Unsymmetrical cyclotriazadisulfonamide (CADA) compounds as human CD4 receptor down-modulating agents. J. Med. Chem. 2011, 54, 5712-5721.

Jenabian, M.-A.; Saïdi, H.; Charpentier, C.; Bouhlal, H.; Schols, D.; Balzarini, J.; Bell, T. W.; Vanham, G.; Bélec, L. Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization. AIDS Res. Ther. 2010, 7, 16-23.

Bell, T. W. Drugs for hepatitis C: unlocking a new mechanism of action. ChemMedChem 2010, 5, 1663-1665.

Vermeire, K.; Van Laethem, K.; Janssens, W.; Bell, T. W.; Schols, D. Human immunodeficiency virus type 1 escape from cyclotriazadisulfonamide-induced CD4-targeted entry inhibition is associated with increased neutralizing antibody susceptibility. J. Virology 2009, 83, 9577-9583.

Bell, T. W.; Cline, J. I. Chemical Evolution II: From Origins of Life to Modern Society. In Molecular Machines; Natural and Artificial Molecular Motors; Friedrich, J. M., Seidel, S. R., Zaikowski, L., Eds.; ACS Books: Washington, D.C., 2009; pp 233-248.

Vermeire, K.; Brouwers, J.; Van Herrewege, Y.; Le Grand, R.; Vanham, G.; Augustijns, P.; Bell, T. W.; Schols, D. CADA, a potential anti-HIV microbicide that specifically targets the cellular CD4 receptor. Curr. HIV Res. 2008, 6, 246-256.

Vermeire, K.; Lisco, A.; Grivel, J.-C.; Scarbrough, E.; Dey, K.; Duffy, N.; Margolis, L.; Bell, T. W.; Schols, D. Design and cellular kinetics of dansyl-labeled CADA derivatives with anti-HIV and CD4 receptor down-modulating activity. Biochem. Pharmacol. 2007, 74, 566-578.

Choi, H.-J.; Park, Y. S.; Kim, M. G.; Park, Y. J.; Yoon, N. S.; Bell, T. W. A D2 symmetric tetraamide macrocycle based on 1,10,4,40-tetrahydro[3,30(2H,20H)-spirobiquinoline]-2,20-dione: Synthesis and selectivity for lithium over sodium and alkaline earth ions. Tetrahedron 2006, 8696-8701.

Vermeire, K.; Schols, D.; Bell, T. W. CD4-targeted HIV inhibitors. Curr. Med. Chem. 2006, 13, 731-743.

Bell, T. W.; Anugu, S.; Bailey, P.; Catalano, V. J.; Dey, K.; Drew, M. G. B.; Duffy, N. H.; Jin, Q.; Samala, M. F.; Sodoma, A.; Welch, W. H.; Schols, D.; Vermeire, K. Synthesis and structure-activity relationship studies of CD4 down-modulating cyclotriazadisulfonamide (CADA) analogs. J. Med. Chem. 2006, 49, 1291-1312.

Barr, J. W.; Bell, T. W.; Catalano, V. J.; Cline, J. I.; Phillips, D. J.; Procupez, R. Syntheses, structures, and photoisomerization of (E)- and (Z)-2-tert-butyl-9-(2,2,2)-triphenyethylidenefluorene. J. Phys. Chem. A 2005, 109, 11650-11654.

Vermeire, K.; Schols, D.; Bell, T. W. CD4 down-modulating compounds with potent anti-HIV activity. Curr. Pharm. Des. 2004, 10, 1795-1803.

Vermeire, K.; Princen, K.; Hatse, S.; De Clercq, E.; Dey, K.; Bell, T. W.; Schols, D. CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV drugs in vitro. AIDS 2004, 18, 2115-2125.

Bell, T.W.; Choi, H.-J.; Harte, W.; Drew, M.G.B. Syntheses, conformations, and basicities of bicyclic triamines. J. Am. Chem. Soc. 2003, 125, 12196-12210.