Ph.D., University of North Carolina, Chapel Hill
Biochemistry, Medicinal, Organic and General Chemistry

Our current interests are in the design and synthesis of pyrrole N- and C-nucleosides. These new nucleoside analogs are derivatives of marine natural products, which have been shown to have potent cytotoxicity. The nucleosides are designed to inhibit IMP dehydrogenase. This inhibition will slow cell replication, which may make the new compounds active anticancer or antiviral agents. These compounds are, in part, modeled after ribavirin, a nucleoside analog of a 5-membered ring heterocycle, which inhibits IMPDH. Ribavirin is useful in treating respiratory syncytial virus and hepatitis C.

Another area of interest is with lipid-lowering agents. The statins are the most widel prescribed drugs for lowering serum cholesterol as a therapy to prevent cardiovascular disease. These drugs lower serum cholesterol through the inhibition of HMG-CoA reductase. While these drugs are potent and effective, they also can have the severe side effects liver damage and rhabdomyolysis. Two of the statins, atorvastatin (Lipitor^®) and fluvastatin (Lescol^®), contain a pyrrole ring. A series of 2,3,4-trisubstituted pyrroles were prepared and found to have lipid-lowering properties in rodents to the same degree as atorvastatin. A key difference in our compounds and the statins is the lack of the chiral 3,5-dihydroxyheptanoic side chain, which defines a drug as a statin. It is anticipated that these new compounds lower serum lipid levels by a different mechanism or do not have the same serious side effects as the statins.

Publications (Bold indicates student author)

• Holub, J.M.; O'Toole-Colin, K.; Getzel, A.; Argenti, A.; Evans, M.A.; Smith, D.C.; Dalglish, G.A.; Rifat, S.; Wilson, D.L.; Taylor, B.M.; Miott, U.; Glersaye, J.; Lam, S.K.; McCranor, B.J.; Berkowitz, J.D.; Miller, R.B.; Lukens, J.R.; Krumpe, K.; Gupton, J.T.; Burnham, B.S. "Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-arylpyrrole-4-carboxylates." Molecules 2004, 9, 134-157.
• Holub, J.M.; Smith, D.C.; Evans, M.A.; Rifat, S.; Argenti, A.; Dalglish, G.A.; Wilson, D.L.; Taylor, B.M.; Berkowitz, J.D.; Krumpe, K.; Gupton, J.T.; Burnham, B.S. "Synthesis and Cytotoxicity of Substituted Ethyl 2-phenacyl-3-phenylpyrrole-4-carboxylates." Arch. Pharm. Pharm. Med. Chem. 2002 (In Preparation)
• Burnham, B.S. "The Synthesis and Pharmacological Activity of Amine-Boranes." Current Medicinal Chemistry 2002 (In Preparation).
• Evans, M.A.; Smith, D.C.; Holub, J.M.; Argenti, A.; Hoff, M.; Dalglish, G.A.; Wilson, D.L.; Taylor, B.M.; Berkowitz, J.D.; Burnham, B.S.; Krumpe, K.; Gupton, J.T.; Scarlett, T.C.; Durham, R.; Hall, I.H. "Synthesis and Cytotoxicity of Substituted Ethyl 2-phenacyl-3-phenylpyrrole-4-carboxylates." Arch. Pharm. Pharm. Med. Chem. 2002 (In Press)
• Scarlett, T.C.; Durham, R.; Hall, I.H.; Crosswicks, R.J.; Berkowitz, J.D.; Burnham, B.S. "Synthesis and Cytotoxicity of Cyanoborane Adducts of N6-Benzoyladenine and 6-Triphenylphosphonylpurine." Metal Based Drugs 2002 (Submitted)
• Gupton, J.T.; Burnham, B.S.; Krumpe, K.E.; Du, K.; Sikorsji, J.A.; Warren, A.E.; Barnes, C.; Hall, I.H. "Synthesis and Cytotoxicity of 2,4-Disubstituted and 2,3,4-Trisubstituted Brominated Pyrroles in Murine and Human Cultured Tumor Cells." Arch. Pharm. Pharm. Med. Chem. 2000, 333, 3-9.
• Gupton, J.T.; Krumpe, K.E.; Burnham, B.S.; Webb, T.; Shuford, R.J.; Sikorski, J. "The Application of Vinylogous Imminium Salt Derivatives to a Regiocontrolled and Efficient Relay Synthesis of Lukianol A and Related Marine Natural Products." Tetrahedron 1999, 55, 14515-14522.
• Gupton, J.T.; Burnham, B.S.; Byrd, B.D.; Krumpe, K.E.; Stokes, C.; Shuford, J.; Winkle, S.; Webb, T.; Warren, A.E.; Barnes, C.; Henry, J.; Hall, I.H. "The Cytotoxicity and Mode of Action of 2,3,4-Trisubstituted Pyrroles and Related Derivatives in Human Tmolt4 Leukemia Cells." Pharmazie 1999, 54, 691-697.
• Burnham, B.S.; Gupton, J.T.; Krumpe, K.E.; Webb, T.; Shuford, J.; Bowers, B.; Warren, A.E.; Barnes, C.; Hall, I.H. "Cytotoxicity of Substituted Alkyl-3,4-bis(4-methoxyphenyl)pyrrole-2-carboxylates in L1210 Lymphoid Leukemia Cells." Arch. Pharm. Pharm. Med. Chem. 1998, 331, 337-341.
• Gupton, J.T.; Krumpe, K.E.; Burnham, B.S.; Dwornik, K.A.; Petrich, S.A.; Du, X.K.; Bruce, M.A.; Vu, P.; Vargas, M.; Keertikar, K.M.; Hosein, K.N.; Jones, C.R.; Sikorski, J.A. "The Application of Disubstituted Vinylogous Iminium Salts and Related Synthons to the Regiocontrolled Preparation of Unsymmetrical 2,3,4-Trisubstituted Pyrroles." Tetrahedron 1998, 45, 5075-5088.

Student Posters at Regional/National Meetings

• Patel, V.; Burnham, B.S. “Progress towards the synthesis of pyrrole nucleoside derivatives of marine natural products.” 239^th National Meeting of the ACS in San Francisco, CA, March 21-25, 2010. 
• Berkowitz, J.D.; Argenti, A.; Crosswicks, R.J.; Evans, M.A.; Burnham, B.S. "Synthesis of Pyrrole C- and N-Nucleosides as Inhibitors of IMP Dehydrogenase." Mid-Atlantic Regional Meeting of the Am. Chemical Soc., George Mason University, Fairfax, Virginia, May 28, 2002.
• Berkowitz, J.D.; Crosswicks, R.J.; Evans, M.A.; Burnham, B.S. "Synthesis of Pyrrole C-Nucleosides as Inhibitors of IMP Dehydrogenase." Mid-Atlantic Regional Meeting of the Am. Chemical Soc., Towson University, Towson, Maryland, May 31, 2001.
• Burnham, B.; Krumpe, K.; Gupton, J.; Byrd, B.; Peaty, N.; Winkel, S.; Shuford, J.; Warren, A.; Barnes, C.; Henry, J.; Hall, I. "Recent Developments Concerning The Antineoplastic Activity and Mode of Action of Pyrrole Derivatives Related to Marine Natural Products." SERMACS'98. Research Triangle Park, NC, November 1998.
• Krumpe, K.; Gupton, J.; Burnham, B.; Holt, H.; Byrd, B.; Winkel, S.; Shuford, J.; Webb, T.; Harrison, A.; Boucher, M.; Hines, I.; Waters, P.; Wright, E.; Peaty, N.; Sikorski, J. "Progress on the Use of Vinylogous Iminium Salt Based Approached as Applied to the Synthesis of Pyrroles Containing Marine Natural Products." SERMACS'98. Research Triangle Park, NC, November 1998.

Project SEED Posters at Regional/National Meetings

• 224th ACS National Meeting in Boston, MA, August 19, 2003. Presented a poster with SEED students Kam S. Lam and Sarah Glersaye and Rider students Kush Patel and Saltanat Najmi. "The Synthesis of Pyrrole C-Nucleosides as Anti-Cancer Agents."
• 220th ACS National Meeting in Washington, DC, August 21, 2000. Presented a poster with SEED students Mafoloe Hoff and Rajmeet Mann and Rider student Richard Crosswicks, "Synthesis of Di- and Trisubstituted Pyrroles and Pyrrole Nucleosides as Anticancer and Hypolipidemic Agents."