Karl Werbovetz

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Karl Werbovetz

Karl Werbovetz, PhD

Title
Professor
Unit / Department / Division
Medicinal Chemistry and Pharmacognosy
Address
Parks Hall
Email Address
Phone Number

Professional Interests

Professional Interests

Parasitic diseases have a devastating effect on public health in developing areas of the world. Research in Karl Werbovetz’s group focuses on the discovery and development of new drug candidates against the protozoan parasitic diseases leishmaniasis, trypanosomiasis, and malaria, with most of our recent efforts concentrating on visceral leishmaniasis (VL) and human African trypanosomiasis (HAT).

Education

  • 1993, PhD, University of Virginia, Chemistry
  • 1988, BS, State University of New York at Binghamton, Chemistry

Honors

  • Distinguished Teaching Award, 2005

Patents

  • 2,5-Diaryl Selenophene Compounds, Aza 2,5-Diaryl Thiophene Compounds, and their Prodrugs as Antiprotozoal Agents (2007, October). WO 2009/051796 A3.
  • Teraryl Components as Antiparasitic Agents (2007, January). US 7964619.
  • 5,5'-Bis-(4-amidinophenyl)-2,2'-bifuran Derivatives and Related Compounds as Antiprotozoal Agents and Prodrugs Thereof (2006, May). 06114189.1.
  • Cationic Substituted Benzofurans as Antimicrobial Agents (2004, December). WO 2005/055935 A3.
  • Reversed Amidines and Methods of Using for Treating, Preventing, or Inhibiting Leishmaniasis (2001, November). WO 02/036588 A3.
  • Controlling Protozoan Infections using Syringomycin-family Lipodepsipeptides (1999, April). US 6310037.

Journal Articles

  • He,Shanshan; Dayton,Alex; Kuppusamy,Periannan; Werbovetz,Karl,A; Drew,Mark,E Induction of Oxidative Stress in Trypanosoma brucei by the Antitrypanosomal Dihydroquinoline OSU-40 Antimicrobial Agents and Chemotherapy. 2012 May; 56(5):2428-2434.
  • Zhu,Xiaohua; Pandharkar,Trupti; Werbovetz,Karl Identification of New Antileishmanial Leads from Hits Obtained by High-Throughput Screening Antimicrobial Agents and Chemotherapy. 2012 Mar; 56(3):1182-1189.
  • Collar,Catharine,J; Zhu,Xiaohua; Werbovetz,Karl; Boykin,David,W; Wilson,W,David Molecular Factors Governing Inhibition of Arylimidamides against Leishmania: Conservative Computational Modeling to Improve Chemotherapies Bioorganic and Medicinal Chemistry. 2011 Aug; 19(15):4552-4561.
  • Endeshaw,Molla,M; Li,Catherine; de Leon,Jessica; Yao,Ni; Latibeaudiere,Kirk; Premalatha,Kokku; Morrissette,Naomi; Werbovetz,Karl,A Synthesis and Evaluation of Oryzalin Analogs against Toxoplasma gondii Bioorganic and Medicinal Chemistry Letters. 2010 Sep; 20(17):5179-5183.
  • Fotie,Jean; Kaiser,Marcel; Delfin,Dawn,A; Manley,Joshua; Reid,Carolyn,S; Paris,Jean-Marc; Wenzler,Tanja; Maes,Louis; Mahasenan,Kiran,V; Li,Chenglong; Werbovetz,Karl,A Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives Journal of Medicinal Chemistry. 2010 Feb; 53(3):966-982.
  • Morgan,Rachel,E; Ahn,Sunnoo; Nzimiro,Sandra; Fotie,Jean; Phelps,Mitch,A; Cotrill,Jeffrey; Yakovich,Adam,J; Sackett,Dan,L; Dalton,James,T; Werbovetz,Karl,A Inhibitors of Tubulin Assembly Identified through Screening a Compound Library Chemical Biology and Drug Design. 2008 Dec; 72(6):513-524.
  • Werbovetz, Karl A. Book review of “Leishmania: After the Genome” ChemMedChem. 2008 Aug; 3 1278-1279.
  • Turabekova,M,A; Vinogradova,V,I; Rasulev,B,F; Levkovich,M,G; Werbovetz,K; Capers,J; Abdullaev,N,D Antiparasitic Activity of Certain Isoquinoline Alkaloids and their Hypothetical Complexes with Oligonucleotides Chemistry of Natural Compounds. 2008 May; 44(3):341-345.
  • George,Tesmol,G; Endeshaw,Molla,M; Morgan,Rachel,E; Mahasenan,Kiran,V; Delfin,Dawn,A; Mukherjee,Mitali,S; Yakovich,Adam,J; Fotie,Jean; Li,Chenglong; Werbovetz,Karl,A Synthesis, Biological Evaluation, and Molecular Modeling of 3,5-Substituted-N-1-phenyl-N-4,N-4-di-n-butylsulfanilamides as Antikinetoplastid Antimicrotubule Agents Bioorganic and Medicinal Chemistry. 2007 Sep; 15(18):6071-6079.
  • Gonzalez,Jose,L; Stephens,Chad,E; Wenzler,Tanja; Brun,Reto; Tanious,Farial,A; Wilson,W,David; Barszcz,Todd; Werbovetz,Karl,A; Boykin,David,W Synthesis and Antiparasitic Evaluation of Bis-2,5-[4-guanidinophenyl]thiophenes European Journal of Medicinal Chemistry. 2007 Apr; 42(4):552-557.
  • Gutteridge,C,E; Vo,J,V; Tillett,C,B; Vigilante,J,A; Dettmer,J,R; Patterson,S,L; Werbovetz,K,A; Capers,J; Nichols,D,A; Bhattacharjee,A,K; Gerena,L Antileishmanial and Antimalarial Chalcones: Synthesis, Efficacy and Cytotoxicity of Pyridinyl and Naphthalenyl Analogs Medicinal Chemistry. 2007 Mar; 3(2):115-119.
  • George, Tesmol, G; Endeshaw, Molla, M; Morgan, Rachel, E; Mahasenan, Kiran, V; Delfin, Dawn, A; Mukherjee, Mitali, S; Yakovich, Adam, J; Fotie, Jean; Li, Chenglong; Werbovetz, Karl A Synthesis, biological evaluation, and molecular modeling of 3,5-substituted-N1-phenyl-N4,N4-di-n-butylsulfanilamides as antikinetoplastid antimicrotubule agents. Bioorganic & medicinal chemistry. 2007 Jan; 15(18):6071-9.
  • Bakunova, S; Bakunov, S; Wenzler, T; Barszcz, T; Werbovetz, K; Brun, R; Hall, J; Tidwell, R Synthesis and In Vitro Antiprotozoal Activity of Bisbenzofuran Cations J. Med. Chem. 2007 Jan;
  • Yakovich,Adam,J; Ragone,Frank,L; Alfonzo,Juan,D; Sackett,Dan,L; Werbovetz,Karl,A Leishmania tarentolae: Purification and Characterization of Tubulin and its Suitability for Antileishmanial Drug Screening Experimental Parasitology. 2006 Dec; 114(4):289-296.
  • Wu,Di; George,Tesmol,G; Hurh,Eunju; Werbovetz,Karl,A; Dalton,James,T Pre-systemic Metabolism Prevents in Vivo Antikinetoplastid Activity of N1, N4-substituted-3,5 Dinitro Sulfanilamide, GB-II-150 Life Sciences. 2006 Aug; 79(11):1081-1093.
  • George,Tesmol,G; Johnsamuel,Jayaseharan; Delfin,Dawn,A; Yakovich,Adam; Mukherjee,Mitali; Phelps,Mitch,A; Dalton,James,T; Sackett,Dan,L; Kaiser,Marcel; Brun,Reto; Werbovetz,Karl,A Antikinetoplastid Antimitotic Activity and Metabolic Stability of Dinitroaniline Sulfonamides and Benzamides Bioorganic and Medicinal Chemistry. 2006 Aug; 14(16):5699-5710.
  • Delfin,Dawn,A; Bhattacharjee,Apurba,K; Yakovich,Adam,J; Werbovetz,Karl,A Activity of and Initial Mechanistic Studies on a Novel Antileishmanial Agent Identified through in Silico Pharmacophore Development and Database Searching Journal of Medicinal Chemistry. 2006 Jul; 49(14):4196-4207.
  • Li,P,K; Pandit,B; Sackett,D,L; Hu,Z,G; Zink,J; Zhi,J,D; Freeman,D; Robey,R,W; Werbovetz,K; Lewis,A; Li,C,L A Thalidomide Analogue with in Vitro Antiproliferative, Antimitotic, and Microtubule-stabilizing Activities Molecular Cancer Therapeutics. 2006 Feb; 5(2):450-456.
  • Werbovetz,K Diamidines as Antitrypanosomal, Antileishmanial and Antimalarial Agents Current Opinion in Investigational Drugs. 2006 Feb; 7(2):147-157.
  • Salem,M,M; Werbovetz,K,A Isoflavonoids and Other Compounds from Psorothamnus arborescens with Antiprotozoal Activities Journal of Natural Products. 2006 Jan; 69(1):43-49.
  • Yakovich, Adam, J; Ragone, Frank, L; Alfonzo, Juan, D; Sackett, Dan, L; Werbovetz, Karl A Leishmania tarentolae: purification and characterization of tubulin and its suitability for antileishmanial drug screening. Experimental parasitology. 2006 Jan; 114(4):289-96.
  • George, Tesmol, G; Johnsamuel, Jayaseharan; Delfin, Dawn, A; Yakovich, Adam; Mukherjee, Mitali; Phelps, Mitch, A; Dalton, James, T; Sackett, Dan, L; Kaiser, Marcel; Brun, Reto; Werbovetz, Karl A Antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides. Bioorganic & medicinal chemistry. 2006 Jan; 14(16):5699-710.
  • Li, Pui-Kai; Pandit, Bulbul; Sackett, Dan, L; Hu, Zhigen; Zink, Jennifer; Zhi, Jiandong; Freeman, Dena; Robey, Robert, W; Werbovetz, Karl; Lewis, Andrew; Li, Chenglong A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities. Molecular cancer therapeutics. 2006 Jan; 5(2):450-6.
  • Das, Umashankar; Gul, H Inci; Alcorn, Jane; Shrivastav, Anuraag; George, Theresa; Sharma, Rajendra, K; Nienaber, Kurt, H; De Clercq, Erik; Balzarini, Jan; Kawase, Masami; Kan, Noriyuki; Tanaka, Toru; Tani, Satoru; Werbovetz, Karl, A; Yakovich, Adam, J; Manavathu, Elias, K; Stables, James, P; Dimmock, Jonathan R Cytotoxic 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienes mounted on alicyclic scaffolds. European journal of medicinal chemistry. 2006 Jan; 41(5):577-85.
  • Salem, Manar, M; Werbovetz, Karl A Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomiasis. Current medicinal chemistry. 2006 Jan; 13(21):2571-98.
  • Werbovetz, Karl Diamidines as antitrypanosomal, antileishmanial and antimalarial agents. Current opinion in investigational drugs (London, England : 2000). 2006 Jan; 7(2):147-57.
  • Li,P,K; Xiao,Z,L; Hu,Z,G; Pandit,B; Sun,Y,J; Sackett,D,L; Werbovetz,K; Lewis,A; Johnsamuel,J Conformationally Restricted Analogs of Combretastatin A-4 Derived from SU5416 Bioorganic and Medicinal Chemistry Letters. 2005 Dec; 15(24):5382-5385.
  • Li, Pui-Kai; Xiao, Zili; Hu, Zhigen; Pandit, Bulbul; Sun, Yanjun; Sackett, Dan, L; Werbovetz, Karl; Lewis, Andrew; Johnsamuel, Jayasekar Conformationally restricted analogs of Combretastatin A-4 derived from SU5416. Bioorganic & medicinal chemistry letters. 2005 Jan; 15(24):5382-5.
  • Salem, Manar, M; Werbovetz, Karl A Antiprotozoal compounds from Psorothamnus polydenius. Journal of natural products. 2005 Jan; 68(1):108-11.
  • Cottrell,D,M; Capers,J; Salem,M,M; DeLuca-Fradley,K; Croft,S,L; Werbovetz,K,A Antikinetoplastid Activity of 3-Aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles Bioorganic and Medicinal Chemistry. 2004 Jun; 12(11):2815-2824.
  • Bhattacharya, Gautam; Herman, Johnathan; Delfin, Dawn; Salem, Manar, M; Barszcz, Todd; Mollet, Mike; Riccio, Guy; Brun, Reto; Werbovetz, Karl A Synthesis and antitubulin activity of N1- and N4-substituted 3,5-dinitro sulfanilamides against African trypanosomes and Leishmania. Journal of medicinal chemistry. 2004 Jan; 47(7):1823-32.
  • Jiang, David, W; Werbovetz, Karl, A; Varadhachary, Atul; Cole, Robert, N; Englund, Paul T Purification and identification of a fatty acyl-CoA synthetase from Trypanosoma brucei. Molecular and biochemical parasitology. 2004 Jan; 135(1):149-52.
  • Hua,D,H; Tamura,M; Egi,M; Werbovetz,K; Delfin,D; Salem,M; Chiang,P,K Antiprotozoal Activities of Symmetrical Bishydroxamic Acids Bioorganic and Medicinal Chemistry. 2003 Oct; 11(20):4357-4361.
  • Werbovetz, Karl, A; Sackett, Dan, L; Delfin, Dawn; Bhattacharya, Gautam; Salem, Manar; Obrzut, Tomasz; Rattendi, Donna; Bacchi, Cyrus Selective antimicrotubule activity of N1-phenyl-3,5-dinitro-N4,N4-di-n-propylsulfanilamide (GB-II-5) against kinetoplastid parasites. Molecular pharmacology. 2003 Jan; 64(6):1325-33.
  • Stephens, Chad, E; Brun, Reto; Salem, Manar, M; Werbovetz, Karl, A; Tanious, Farial; Wilson, W David; Boykin, David W The activity of diguanidino and 'reversed' diamidino 2,5-diarylfurans versus Trypanosoma cruzi and Leishmania donovani. Bioorganic & medicinal chemistry letters. 2003 Jan; 13(12):2065-9.
  • Werbovetz,Karl,A Tubulin as an Antiprotozoal Drug Target Mini Reviews in Medicinal Chemistry. 2002 Dec; 2(6):519-529.
  • Bhattacharya,G; Salem,M,M; Werbovetz,K,A Antileishmanial Dinitroaniline Sulfonamides with Activity against Parasite Tubulin Bioorganic and Medicinal Chemistry Letters. 2002 Sep; 12(17):2395-2398.
  • Werbovetz,K,A Promising Therapeutic Targets for Antileishmanial Drugs Expert Opinion on Therapeutic Targets. 2002 Aug; 6(4):407-422.
  • Bhattacharjee,A,K; Skanchy,D,J; Jennings,B; Hudson,T,H; Brendle,J,J; Werbovetz,K,A Analysis of Stereoelectronic Properties, Mechanism of Action and Pharmacophore of Synthetic indolo[2,1-b]quinazoline-6,12-dione Derivatives in Relation to Antileishmanial Activity using Quantum Chemical, Cyclic Voltammetry and 3-D-QSAR CATALYST Procedures Bioorganic and Medicinal Chemistry. 2002 Jun; 10(6):1979-1989.
  • Brendle,J,J; Outlaw,A; Kumar,A; Boykin,D,W; Patrick,D,A; Tidwell,R,R; Werbovetz,K,A Antileishmanial Activities of Several Classes of Aromatic Dications Antimicrobial Agents and Chemotherapy. 2002 Mar; 46(3):797-807.
  • Bhattacharya, Gautam; Salem, Manar, M; Werbovetz, Karl A Antileishmanial dinitroaniline sulfonamides with activity against parasite tubulin. Bioorganic & medicinal chemistry letters. 2002 Jan; 12(17):2395-8.
  • Havens,C,G; Bryant,N; Asher,L; Lamoreaux,L; Perfetto,S; Brendle,J,J; Werbovetz,K,A Cellular Effects of Leishmanial Tubulin Inhibitors on L. donovani Molecular and Biochemical Parasitology. 2000 Oct; 110(2):223-236.
  • Werbovetz,K,A; Bhattacharjee,A,K; Brendle,J,J; Scovill,J,P Analysis of Stereoelectronic Properties of Camptothecin Analogues in Relation to Biological Activity Bioorganic and Medicinal Chemistry. 2000 Jul; 8(7):1741-1747.
  • Werbovetz, K A Target-based drug discovery for malaria, leishmaniasis, and trypanosomiasis. Current medicinal chemistry. 2000 Jan; 7(8):835-60.
  • Havens, C, G; Bryant, N; Asher, L; Lamoreaux, L; Perfetto, S; Brendle, J, J; Werbovetz, K A Cellular effects of leishmanial tubulin inhibitors on L. donovani. Molecular and biochemical parasitology. 2000 Jan; 110(2):223-36.
  • Werbovetz, K, A; Brendle, J, J; Sackett, D L Purification, characterization, and drug susceptibility of tubulin from Leishmania. Molecular and biochemical parasitology. 1999 Jan; 98(1):53-65.
  • Werbovetz,K,A; Brendle,J,J; Sackett,D,L Purification, Characterization, and Drug Susceptibility of Tubulin from Leishmania Molecular and Biochemical Parasitology. 1999 Jan; 98(1):53-65.
  • Pitzer, K, K; Werbovetz, K, A; Brendle, J, J; Scovill, J P Synthesis and biological evaluation of 4-chloro-3, 5-dinitrobenzotrifluoride analogues as antileishmanial agents. Journal of medicinal chemistry. 1998 Jan; 41(24):4885-9.
  • Madalengoitia,J,S; Tepe,J,J; Werbovetz,K,A; Lehnert,E,K; MACDONALD,T,L Structure-activity Relationship for DNA Topoisomerase II-induced DNA Cleavage by Azatoxin Analogues Bioorganic and Medicinal Chemistry. 1997 Sep; 5(9):1807-1815.
  • Werbovetz, K, A; Englund, P T Glycosyl phosphatidylinositol myristoylation in African trypanosomes. Molecular and biochemical parasitology. 1997 Jan; 85(1):1-7.
  • Tepe,J,J; Madalengoitia,J,S; Slunt,K,M; Werbovetz,K,A; Spoors,P,G; MACDONALD,T,L Inhibition of DNA Topoisomerase II by Azaelliptitoxins Functionalized in the Variable Substituent Domain Journal of Medicinal Chemistry. 1996 May; 39(11):2188-2196.
  • Werbovetz, K, A; Bacchi, C, J; Englund, P T Trypanocidal analogs of myristate and myristoyllysophosphatidylcholine. Molecular and biochemical parasitology. 1996 Jan; 81(1):115-8.
  • Werbovetz, K, A; Englund, P T Lipid metabolism in Trypanosoma brucei: utilization of myristate and myristoyllysophosphatidylcholine for myristoylation of glycosyl phosphatidylinositols. The Biochemical journal. 1996 Jan; 318 ( Pt 2) 575-81.
  • Buxbaum, L, U; Milne, K, G; Werbovetz, K, A; Englund, P T Myristate exchange on the Trypanosoma brucei variant surface glycoprotein. Proceedings of the National Academy of Sciences of the United States of America. 1996 Jan; 93(3):1178-83.
  • Werbovetz,K,A; Spoors,P,G; Pearson,R,D; MACDONALD,T,L Cleavable Complex Formation in Leishmania chagasi Treated with Anilinoacridines Molecular and Biochemical Parasitology. 1994 May; 65(1):1-10.
  • Werbovetz, K, A; Spoors, P, G; Pearson, R, D; Macdonald, T L Cleavable complex formation in Leishmania chagasi treated with anilinoacridines. Molecular and biochemical parasitology. 1994 Jan; 65(1):1-10.
  • Doering, T, L; Lu, T; Werbovetz, K, A; Gokel, G, W; Hart, G, W; Gordon, J, I; Englund, P T Toxicity of myristic acid analogs toward African trypanosomes. Proceedings of the National Academy of Sciences of the United States of America. 1994 Jan; 91(21):9735-9.
  • Werbovetz,K,A; Lehnert,E,K; Macdonald,T,L; Pearson,R,D Cytotoxicity of Acridine Compounds for Leishmania Promastigotes in Vitro Antimicrobial Agents and Chemotherapy. 1992 Feb; 36(2):495-497.