|William L. Neumann, Ph.D.
Associate Professor of Pharmaceutical Sciences
Fax: (618) 650‑5145
Organic/Medicinal Chemistry and Chemical Biology
B.S., 1983, University of Missouri Columbia
Ph.D., 1987, University of Missouri St. Louis
Synthetic Organic Chemistry, Medicinal Chemistry, Molecular Pharmacology
Metalloporphyrin and Dipyrromethene-Based Catalytic Antioxidants We have been interested in the development of synthetic metalloenzyme mimics for nearly 20 years now. To this end we are currently developing a series of metal-charge-shielded manganese(III) porphyrin and dipyrromethene derivatives as potent orally active peroxynitrite decomposition catalysts. Peroxynitrite is the short-lived and highly toxic reaction product of superoxide and nitric oxide. It is overproduced in vivo under the conditions of neuroinflammation leading to chronic pain and opioid analgesic tolerance. Our catalysts can destroy peroxynitrite in vivo leading to the attenuation of chronic pain and the reversal of opioid analgesic tolerance. Additionally, our catalysts are effective in other pathologies driven by the over-production of peroxynitrite. To this end, we have active collaborations in the areas of obesity-driven diabetes/metabolic syndrome and chemotherapy-induced peripheral neuropathy.
Synthesis of Heterocyclic Derivatives for Drug Discovery We are currently developing new synthetic routes to pyrrolidine-based heterocyclic systems as scaffold for drug discovery. Our main emphasis is on nitroalkane-cinnamate conjugate addition chemistry and Pd-catalyzed carboamination cascades for the synthesis of benzindole analogues. The resulting compounds are being surveyed for dopaminergic and sigma receptor activity.
Johns, Michael; Fyalka, Robert; Shea, Jennifer A.; Neumann, William L.; Rausaria, Smita; Msengi, Eliwaza Naomi; Imani-Nejad, Maryam; Zollars, Harry; McPherson, Timothy; Schober, Joseph; Wooten, Joshua; Kwon, Guim; “SR-135, a peroxynitrite decomposing catalyst, enhances β-cell function and survival in B6D2F1 mice fed a high fat diet” Archives of Biochemistry and Biophysics 2015, (Ahead of Print).
Janes, Kali; Little, Joshua W.; Li, Chao; Bryant, Leesa; Chen, Collin; Chen, Zhoumou; Kamocki, Krzysztof; Doyle, Timothy; Snider, Ashley; Esposito, Emanuela; Cuzzocrea, Salvatore; Bieberich, Erhard; Obeid, Lina; Petrache, Irina; Nicol, Grant; Neumann, William L.; Salvemini, Daniela. “The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1” J. Biological Chemistry 2014, 289(30), 21082-21097.
Little, Joshua W.; Cuzzocrea, Salvatore; Bryant, Leesa; Esposito, Emanuela; Doyle, Timothy; Rausaria, Smita; Neumann, William L.; Salvemini, Daniela: “Spinal mitochondrial-derived peroxynitrite enhances neuroimmune activation during morphine hyperalgesia and antinociceptive tolerance.” Pain 2013, 154(7), 978-986.
Little, Joshua W.; Chen, Zhoumou; Doyle, Tim; Porreca, Frank; Ghaffari, Mahsa; Neumann, William L.; Salvemini, Daniela: “Supraspinal peroxynitrite modulates pain signaling by suppressing the endogenous opioid pathway.” J. Neuroscience 2012, 32,10797-10808.
Tim Doyle, Zhoumou Chen, Carolina Muscoli, Leesa Bryant, Concetta Dagostino, Jan Ryerse, Smita Rausaria, Andrew Kamadulski, William L. Neumann, and Daniela Salvemini: “Targeting the Overproduction of Peroxynitrite for the Prevention and Reversal of Paclitaxel-induced peripheral neuropathy” J. Neuroscience 2012, 32, 6149-6160.
Kali Janes, William L. Neumann and Daniela Salvemini: “Anti-superoxide and anti-peroxynitrite strategies in pain suppression.” Biochimica et Biophysica Acta, - Molecular Basis of Disease 2012, 1822(5), 815-821.
Rausaria, Smita; Ghaffari, Mahsa M. E.; Kamadulski, Andrew; Rodgers, Kenny; Bryant, Leesa; Chen, Zhoumou; Doyle, Tim; Shaw, Michael J.; Salvemini, Daniela; Neumann, William L. “Retooling Manganese(III) Porphyrin-Based Peroxynitrite Decomposition Catalysts for Selectivity and Oral Activity: A Potential New Strategy for Treating Chronic Pain” J. Med. Chem. 2011, 54, 8658-8669.
Smita Rausaria, Andrew Kamadulski, Nigam P. Rath, Leesa Bryant, Zhoumou Chen, Daniela Salvemini, and William L. Neumann. Manganese(III) Complexes of Bis-(hydroxyphenyl)-dipyrromethenes are Potent Orally Active Peroxynitrite Scavengers J. Am. Chem. Soc. 2011, 133, 4200-4203.
Daniela Salvemini, Joshua W. Little, Timothy Doyle, William Neumann. “Roles of Reactive Oxygen and Nitrogen Species in Pain.” Free Rad. Biol. Med. 2011,51, 951-966.
Porphyrin-crosslinked Block Copolymer Assemblies as Photophysically-active Nanoscopic Devices. Jennifer L. Sorrells, Ritu Shrestha, William L. Neumann, and Karen L. Wooley. J. Mater. Chem. 2010, 21, 8983-8986.
Counter-Regulation of Opioid Analgesia by Glial-Derived Bioactive Sphingolipids. Muscoli C, Doyle T, Dagostino C, Bryant L, Chen Z, Watkins LR, Ryerse J, Bieberich E, Neumman W, Salvemini D. J. Neurosci. 2010, Nov 17;30(46):15400-15408.
ω-Oxidation of α-chlorinated fatty acids: Identification of α-chlorinated dicarboxylic acids. Viral V. Brahmbhatt, Carolyn J. Albert, Dhanalakshmi S. Anbukumar, Bryce A. Cunningham, William L. Neumann, David A. Ford, J. Biol. Chem. 2010, 285, 41255-41269.
Chlorinated lipid species in activated human neutrophils: lipid metabolites of 2-chlorohexadecanal, Anbukumar, Dhanalakshmi S.; Shornick, Laurie P.; Albert, Carolyn J.; Steward, Melissa M.; Zoeller, Raphael A.; Neumann, William L.; Ford, David A. Journal of Lipid Research 2010, 51(5), 1085-1092.
William L. Neumann, Daniela Salvemini. Targeting peroxynitrite driven nitroxidative stress with synzymes: A novel therapeutic approach in chronic pain management, IUBMB Life Sciences, 2010, 86, 604-614.
William L. Neumann, Daniela Salvemini. Peroxynitrite: A Strategic Linchpin of Opioid Analgesic Tolerance. Trends in Pharmacological Sciences, 2009, 30, 194-202.