Karl Werbovetz, PhD

Professor

Medicinal Chemistry and Pharmacognosy

Research Areas: Infectious Diseases, Division of Medicinal Chemistry & Pharmacognosy

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

Publications

Imidazoles as Potential Anticancer Agents: An Update on Recent Studies, Molecules. 2021 Jul | journal-article. doi: 10.3390/molecules26144213.
Synthesis and Antileishmanial Evaluation of Arylimidamide–Azole Hybrids Containing a Phenoxyalkyl Linker, ACS Infectious Diseases. 2021 Feb | journal-article. doi: 10.1021/acsinfecdis.0c00855.
Synthesis and antileishmanial evaluation of thiazole orange analogs, Bioorganic & Medicinal Chemistry Letters. 2020 Jan | journal-article. doi: 10.1016/j.bmcl.2019.126725.
Microneedle-Based Delivery of Amphotericin B for Treatment of Cutaneous Leishmaniasis, Biomedical Microdevices. 2019 Jan | journal-article. doi: 10.1007/s10544-018-0355-8.
Antileishmanial Efficacy and Pharmacokinetics of DB766-Azole Combinations, Antimicrobial Agents and Chemotherapy. 2018 Jan | journal-article. doi: 10.1128/aac.01129-17.
Correction for Pandharkar et al., “Studies on the Antileishmanial Mechanism of Action of the Arylimidamide DB766: Azole Interactions and Role of CYP5122A1”, Antimicrobial Agents and Chemotherapy. 2018 Jan | journal-article. doi: 10.1128/aac.01124-17.
Synthesis and pharmacological evaluation of mono-arylimidamides as antileishmanial agents, Bioorganic & Medicinal Chemistry Letters. 2016 May | journal-article. doi: 10.1016/j.bmcl.2016.03.082.
Correction to Antileishmanial Activity of a Series of N2,N4-Disubstituted Quinazoline-2,4-diamines, Journal of Medicinal Chemistry. 2016 Jan | journal-article. doi: 10.1021/acs.jmedchem.5b00981.
Antileishmanial activity of some abietane diterpenoids from the cones of bald cypress, Taxodium distichum, Planta Medica. 2014 Jul | journal-article. doi: 10.1055/s-0034-1382490.
Studies on the Antileishmanial Mechanism of Action of the Arylimidamide DB766: Azole Interactions and Role of CYP5122A1, Antimicrobial Agents and Chemotherapy. 2014 Jun | journal-article. doi: 10.1128/aac.02405-14.
Antileishmanial Activity of a Series of N2,N4-Disubstituted Quinazoline-2,4-diamines, Journal of Medicinal Chemistry. 2014 Jun | journal-article. doi: 10.1021/jm5000408.
Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro, International Journal of Toxicology. 2014 May | journal-article. doi: 10.1177/1091581814533971.
Synthesis and antiprotozoal activities of benzyl phenyl ether diamidine derivatives, European Journal of Medicinal Chemistry. 2013 Sep | journal-article. doi: 10.1016/j.ejmech.2013.06.033.
Discovery of benzamide analogs as negative allosteric modulators of human neuronal nicotinic receptors: Pharmacophore modeling and structure–activity relationship studies, Bioorganic & Medicinal Chemistry. 2013 Aug | journal-article. doi: 10.1016/j.bmc.2013.03.082.
Antileishmanial Activity of Some Abietane Diterpenoids from Taxodium distichum, Planta Medica. 2013 Jul | journal-article. doi: 10.1055/s-0033-1348695.
Synthesis and Antiprotozoal Activity of Dicationic m-Terphenyl and 1,3-Dipyridylbenzene Derivatives, Journal of Medicinal Chemistry. 2013 Jun | journal-article. doi: 10.1021/jm400508e.
Novel amidines and analogues as promising agents against intracellular parasites: a systematic review, Parasitology. 2013 Apr | journal-article. doi: 10.1017/s0031182013000292.
8,8-Dialkyldihydroberberines with Potent Antiprotozoal Activity, Journal of Natural Products. 2012 Nov | journal-article. doi: 10.1021/np300638f.
Antileishmanial bis-arylimidamides: DB766 analogs modified in the linker region and bis-arylimidamide structure–activity relationships, Bioorganic & Medicinal Chemistry Letters. 2012 Nov | journal-article. doi: 10.1016/j.bmcl.2012.06.037.
Synthesis, DNA binding and antileishmanial activity of low molecular weight bis-arylimidamides, European Journal of Medicinal Chemistry. 2012 Sep | journal-article. doi: 10.1016/j.ejmech.2012.06.058.
Induction of Oxidative Stress in Trypanosoma brucei by the Antitrypanosomal Dihydroquinoline OSU-40, Antimicrobial Agents and Chemotherapy. 2012 Feb | journal-article. doi: 10.1128/aac.06386-11.
Molecular factors governing inhibition of arylimidamides against Leishmania: Conservative computational modeling to improve chemotherapies, Bioorganic & Medicinal Chemistry. 2011 Aug | journal-article. doi: 10.1016/j.bmc.2011.06.026.
Correction to Synthesis and Antiprotozoal Activity of Cationic 1,4-Diphenyl-1H-1,2,3-triazoles, Journal of Medicinal Chemistry. 2011 May | journal-article. doi: 10.1021/jm2005282.
Potent antiprotozoal activity of a novel semi-synthetic berberine derivative, Bioorganic & Medicinal Chemistry Letters. 2011 May | journal-article. doi: 10.1016/j.bmcl.2011.01.101.
Structure-Activity Relationship Investigations Of Leishmanicidal N-Benzylcytisine Derivatives, Chemical Biology & Drug Design. 2011 May | journal-article. doi: 10.1111/j.1747-0285.2011.01092.x.
Antiparasitic Activity of C-Geranyl Flavonoids from Mimulus bigelovii, Phytotherapy Research. 2011 Feb | journal-article. doi: 10.1002/ptr.3404.
Simultaneous Determination of A Novel Antitrypanosomal Compound (OSU-36) and its Ester Derivative (OSU-40) in Plasma by HPLC: Application to First Pharmacokinetic Study in Rats, Journal of Pharmacy & Pharmaceutical Sciences. 2011 Jan | journal-article. doi: 10.18433/j3cp4s.
Identification of New Antileishmanial Leads from Hits Obtained by High-Throughput Screening, Antimicrobial Agents and Chemotherapy. 2011 Jan | journal-article. doi: 10.1128/aac.05412-11.
Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii, Bioorganic & Medicinal Chemistry Letters. 2010 Sep | journal-article. doi: 10.1016/j.bmcl.2010.07.003.
New antileishmanial candidates and lead compounds, Current Opinion in Chemical Biology. 2010 Aug | journal-article. doi: 10.1016/j.cbpa.2010.03.023.
Dinitroaniline Activity in Toxoplasma gondii Expressing Wild-Type or Mutant α-Tubulin, Antimicrobial Agents and Chemotherapy. 2010 Apr | journal-article. doi: 10.1128/aac.01150-09.
Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives, Journal of Medicinal Chemistry. 2010 Jan | journal-article. doi: 10.1021/jm900723w.
A Novel Tropically Stable Oral Amphotericin B Formulation (iCo-010) Exhibits Efficacy against Visceral Leishmaniasis in a Murine Model, PLoS Neglected Tropical Diseases. 2010 Jan | journal-article. doi: 10.1371/journal.pntd.0000913.
Isolating Tubulin from Nonneural Sources, Methods in Cell Biology. 2010 Jan | other. doi: 10.1016/s0091-679x(10)95002-4.
α-Tubulin Mutations Alter Oryzalin Affinity and Microtubule Assembly Properties To Confer Dinitroaniline Resistance, Eukaryotic Cell. 2010 Jan | journal-article. doi: 10.1128/ec.00140-10.
Synthesis and Antiprotozoal Activity of Cationic 1,4-Diphenyl-1H-1,2,3-triazoles, Journal of Medicinal Chemistry. 2009 Nov | journal-article. doi: 10.1021/jm901178d.
Synthesis and antiprotozoal activities of dicationic bis(phenoxymethyl)benzenes, bis(phenoxymethyl)naphthalenes, and bis(benzyloxy)naphthalenes, European Journal of Medicinal Chemistry. 2009 Sep | journal-article. doi: 10.1016/j.ejmech.2009.03.014.
Synthesis and Antiprotozoal Properties of Pentamidine Congeners Bearing the Benzofuran Motif, Journal of Medicinal Chemistry. 2009 Aug | journal-article. doi: 10.1021/jm9006406.
Highly Effective Oral Amphotericin B Formulation against Murine Visceral Leishmaniasis, The Journal of Infectious Diseases. 2009 Aug | journal-article. doi: 10.1086/600105.
Synthesis and Antiprotozoal Activity of Pyridyl Analogues of Pentamidine, Journal of Medicinal Chemistry. 2009 Jul | journal-article. doi: 10.1021/jm900805v.
Structure−Activity Study of Pentamidine Analogues as Antiprotozoal Agents, Journal of Medicinal Chemistry. 2009 Mar | journal-article. doi: 10.1021/jm801547t.
Redox-active dinitrodiphenylthioethers against Leishmania: Synthesis, structure–activity relationships and mechanism of action studies, Bioorganic & Medicinal Chemistry. 2009 Jan | journal-article. doi: 10.1016/j.bmc.2008.11.031.
Visceral leishmaniasis affects liver and spleen concentrations of amphotericin B following administration to mice, Journal of Antimicrobial Chemotherapy. 2009 Jan | journal-article. doi: 10.1093/jac/dkp465.
Pharmacological and biological screening of ascorbigen: protection against glucose-induced endothelial cell toxicity, Phytotherapy Research. 2008 Oct | journal-article. doi: 10.1002/ptr.2494.
Synthesis and Antiprotozoal Activity of Cationic 2-Phenylbenzofurans, Journal of Medicinal Chemistry. 2008 Oct | journal-article. doi: 10.1021/jm800918v.
Antiparasitic activity of certain isoquinoline alkaloids and their hypothetical complexes with oligonucleotides, Chemistry of Natural Compounds. 2008 Oct | journal-article. doi: 10.1007/s10600-008-9057-4.
Inhibition by Dications of In Vitro Growth of Leishmania major and Leishmania tropica: Causative Agents of Old World Cutaneous Leishmaniasis, Journal of Parasitology. 2008 Jun | journal-article. doi: 10.1645/ge-1387.1.
Flavylium Salts as Precursors of Biologically Active Chalcones, Letters in Drug Design & Discovery. 2008 Jan | journal-article. doi: 10.2174/157018008783406697.
Azaterphenyl diamidines as antileishmanial agents, Bioorganic & Medicinal Chemistry Letters. 2008 Jan | journal-article. doi: 10.1016/j.bmcl.2007.10.091.
Inhibition by Dications of In Vitro Growth of Leishmania major and Leishmania tropica: Causative Agents of Old World Cutaneous Leishmaniasis, Journal of Parasitology. 2008 Jan | journal-article. doi: 10.1645/ge-1387r1.1.
Inhibitors of Tubulin Assembly Identified through Screening a Compound Library, Chemical Biology & Drug Design. 2008 Jan | journal-article. doi: 10.1111/j.1747-0285.2008.00729.x.
Synthesis and in Vitro Antiprotozoal Activity of Bisbenzofuran Cations, Journal of Medicinal Chemistry. 2007 Oct | journal-article. doi: 10.1021/jm0708634.
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 Sep | journal-article. doi: 10.1016/j.bmc.2007.06.042.
Synthesis and antiparasitic evaluation of bis-2,5-[4-guanidinophenyl]thiophenes, European Journal of Medicinal Chemistry. 2007 Apr | journal-article. doi: 10.1016/j.ejmech.2006.11.006.
Antileishmanial and Antimalarial Chalcones: Synthesis, Efficacy and Cytotoxicity of Pyridinyl and Naphthalenyl Analogs, Medicinal Chemistry. 2007 Mar | journal-article. doi: 10.2174/157340607780059530.
Natural Products from Plants as Drug Candidates and Lead Compounds Against Leishmaniasis and Trypanosomiasis, Current Medicinal Chemistry. 2006 Sep | journal-article. doi: 10.2174/092986706778201611.
Antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides, Bioorganic & Medicinal Chemistry. 2006 Aug | journal-article. doi: 10.1016/j.bmc.2006.04.017.
Pre-systemic metabolism prevents in vivo antikinetoplastid activity of N1,N4-substituted 3,5-dinitro sulfanilamide, GB-II-150, Life Sciences. 2006 Aug | journal-article. doi: 10.1016/j.lfs.2006.03.028.
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 Jun | journal-article. doi: 10.1021/jm060156v.
A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities, Molecular Cancer Therapeutics. 2006 Feb | journal-article. doi: 10.1158/1535-7163.mct-05-0254.
Leishmania tarentolae: Purification and characterization of tubulin and its suitability for antileishmanial drug screening, Experimental Parasitology. 2006 Jan | journal-article. doi: 10.1016/j.exppara.2006.04.008.
Activity of Amidine-containing Diphenylureas Against P. falciparum, Letters in Drug Design & Discovery. 2005 Mar | journal-article. doi: 10.2174/1570180053175061.
Promising therapeutic targets for antileishmanial drugs, Expert Opinion on Therapeutic Targets. 2005 Feb | journal-article. doi: 10.1517/14728222.6.4.407.
Conformationally restricted analogs of Combretastatin A-4 derived from SU5416, Bioorganic & Medicinal Chemistry Letters. 2005 Jan | journal-article. doi: 10.1016/j.bmcl.2005.09.001.
Isoflavonoids and Other Compounds from Psorothamnus arborescens with Antiprotozoal Activities, Journal of Natural Products. 2005 Jan | journal-article. doi: 10.1021/np0502600.
Antikinetoplastid activity of 3-aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles, Bioorganic & Medicinal Chemistry. 2004 Jun | journal-article. doi: 10.1016/j.bmc.2004.03.054.
Purification and identification of a fatty acyl-CoA synthetase from Trypanosoma brucei, Molecular and Biochemical Parasitology. 2004 May | journal-article. doi: 10.1016/j.molbiopara.2004.01.003.
SYNTHESIS OF DICATIONIC 2,5-DIARYLPYRROLES, Heterocyclic Communications. 2004 Jan | journal-article. doi: 10.1515/hc.2004.10.6.423.
Antiprotozoal Compounds from Psorothamnus polydenius, Journal of Natural Products. 2004 Jan | journal-article. doi: 10.1021/np049682k.
Selective Antimicrotubule Activity ofN1-Phenyl-3,5-dinitro-N4,N4-di-n-propylsulfanilamide (GB-II-5) against Kinetoplastid Parasites, Molecular Pharmacology. 2003 Nov | journal-article. doi: 10.1124/mol.64.6.1325.
Antiprotozoal activities of symmetrical bishydroxamic acids, Bioorganic & Medicinal Chemistry. 2003 Oct | journal-article. doi: 10.1016/s0968-0896(03)00522-4.
Antileishmanial dinitroaniline sulfonamides with activity against parasite tubulin, Bioorganic & Medicinal Chemistry Letters. 2002 Sep | journal-article. doi: 10.1016/s0960-894x(02)00465-1.
Antileishmanial Activities of Several Classes of Aromatic Dications, Antimicrobial Agents and Chemotherapy. 2002 Mar | journal-article. doi: 10.1128/aac.46.3.797-807.2002.
Tubulin as an Antiprotozoal Drug Target, Mini-Reviews in Medicinal Chemistry. 2002 Jan | journal-article. doi: 10.2174/1389557023405648.
Selective Lead Compounds against Kinetoplastid Tubulin, Advances In Experimental Medicine And Biology. 1 Jan | other. doi: 10.1007/978-0-387-77570-8_4.
Cellular effects of leishmanial tubulin inhibitors on L. donovani, Molecular and Biochemical Parasitology. 2000 Oct | journal-article. doi: 10.1016/s0166-6851(00)00272-3.
Target-Based Drug Discovery for Malaria, Leishmaniasis, and Trypanosomiasis, Current Medicinal Chemistry. 2000 Aug | journal-article. doi: 10.2174/0929867003374615.
Analysis of stereoelectronic properties of camptothecin analogues in relation to biological activity, Bioorganic & Medicinal Chemistry. 2000 Jul | journal-article. doi: 10.1016/s0968-0896(00)00111-5.
Purification, characterization, and drug susceptibility of tubulin from Leishmania, Molecular and Biochemical Parasitology. 1999 Jan | journal-article. doi: 10.1016/s0166-6851(98)00146-7.
Synthesis and Biological Evaluation of 4-Chloro-3,5-dinitrobenzotrifluoride Analogues as Antileishmanial Agents, Journal of Medicinal Chemistry. 1998 Nov | journal-article. doi: 10.1021/jm9804073.
Structure-activity relationship for DNA topoisomerase II-induced DNA cleavage by azatoxin analogues, Bioorganic & Medicinal Chemistry. 1997 Sep | journal-article. doi: 10.1016/s0968-0896(97)00113-2.
Glycosyl phosphatidylinositol myristoylation in African trypanosomes, Molecular and Biochemical Parasitology. 1997 Mar | journal-article. doi: 10.1016/s0166-6851(96)02820-4.
Trypanocidal analogs of myristate and myristoyllysophosphatidylcholine, Molecular and Biochemical Parasitology. 1996 Oct | journal-article. doi: 10.1016/0166-6851(96)02708-9.
Lipid metabolism in Trypanosoma brucei: utilization of myristate and myristoyllysophosphatidylcholine for myristoylation of glycosyl phosphatidylinositols, Biochemical Journal. 1996 Sep | journal-article. doi: 10.1042/bj3180575.
Inhibition of DNA Topoisomerase II by Azaelliptitoxins Functionalized in the Variable Substituent Domain, Journal of Medicinal Chemistry. 1996 May | journal-article. doi: 10.1021/jm9508806.
Myristate exchange on the Trypanosoma brucei variant surface glycoprotein., Proceedings of the National Academy of Sciences. 1996 Feb | journal-article. doi: 10.1073/pnas.93.3.1178.
Toxicity of myristic acid analogs toward African trypanosomes., Proceedings of the National Academy of Sciences. 1994 Oct | journal-article. doi: 10.1073/pnas.91.21.9735.
On the mechanism of arylamine-DNA adduct formation, Bioorganic & Medicinal Chemistry Letters. 1994 Oct | journal-article. doi: 10.1016/0960-894x(94)85033-x.
Cleavable complex formation in Leishmania chagasi treated with anilinoacridines, Molecular and Biochemical Parasitology. 1994 May | journal-article. doi: 10.1016/0166-6851(94)90110-4.
Cytotoxicity of acridine compounds for Leishmania promastigotes in vitro, Antimicrobial Agents and Chemotherapy. 1992 Feb | journal-article. doi: 10.1128/aac.36.2.495.
Treatment of leishmaniasis and trypanosomiasis, Current Opinion in Infectious Diseases. 1992 Jan | journal-article. doi: 10.1097/00001432-199212000-00015.
Tubulin binding of conformationally restricted bis-aryl compounds, Bioorganic & Medicinal Chemistry Letters. 1991 Jan | journal-article. doi: 10.1016/s0960-894x(01)81034-9.