trypanocidal agents

Summary

Summary: Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA.

Top Publications

  1. pmc High-throughput decoding of antitrypanosomal drug efficacy and resistance
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nature 482:232-6. 2012
  2. ncbi Human African trypanosomiasis
    Reto Brun
    Swiss Tropical Institute, Basel, Switzerland
    Lancet 375:148-59. 2010
  3. ncbi A critical review on Chagas disease chemotherapy
    José Rodriques Coura
    Departamento de Medicina Tropical, Instituto Oswaldo Cruz FIOCRUZ, Av Brasil 4365, 21045 900 Rio de Janeiro, RJ, Brasil
    Mem Inst Oswaldo Cruz 97:3-24. 2002
  4. ncbi Clinical and epidemiological aspects of Chagas disease
    A Prata
    Tropical Medicine Departament, Faculdade de Medicina do Triangulo Mineiro, Uberaba, MG, Brazil
    Lancet Infect Dis 1:92-100. 2001
  5. ncbi Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis)
    Jose A Castro
    Centro de Investigaciones Toxicológicas CEITOX CITEFA CONICET, J B de La Salle 4397, Villa Martelli, Pcia de Buenos Aires 1603, Argentina
    Hum Exp Toxicol 25:471-9. 2006
  6. pmc State of the art in African trypanosome drug discovery
    Robert T Jacobs
    SCYNEXIS, Inc, Research Triangle Park, North Carolina 27709 2878, USA
    Curr Top Med Chem 11:1255-74. 2011
  7. pmc Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population
    Ana Maria Mejía
    Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, University of London, United Kingdom
    J Infect Dis 206:220-8. 2012
  8. ncbi Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease
    L S Filardi
    Centro de Pesquisas Rene Rachou, FIOCRUZ, Belo Horizonte, Brazil
    Trans R Soc Trop Med Hyg 81:755-9. 1987
  9. ncbi Pathogenesis of chronic Chagas heart disease
    Jose Antonio Marin-Neto
    Cardiology Division, Department of Internal Medicine, Medical School of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
    Circulation 115:1109-23. 2007
  10. ncbi The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease
    Najib M El-Sayed
    Department of Parasite Genomics, Institute for Genomic Research, Rockville, MD 20850, USA
    Science 309:409-15. 2005

Detail Information

Publications275 found, 100 shown here

  1. pmc High-throughput decoding of antitrypanosomal drug efficacy and resistance
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nature 482:232-6. 2012
    ....
  2. ncbi Human African trypanosomiasis
    Reto Brun
    Swiss Tropical Institute, Basel, Switzerland
    Lancet 375:148-59. 2010
    ..WHO has stated that if national control programmes, international organisations, research institutes, and philanthropic partners engage in concerted action, elimination of this disease might even be possible...
  3. ncbi A critical review on Chagas disease chemotherapy
    José Rodriques Coura
    Departamento de Medicina Tropical, Instituto Oswaldo Cruz FIOCRUZ, Av Brasil 4365, 21045 900 Rio de Janeiro, RJ, Brasil
    Mem Inst Oswaldo Cruz 97:3-24. 2002
    ....
  4. ncbi Clinical and epidemiological aspects of Chagas disease
    A Prata
    Tropical Medicine Departament, Faculdade de Medicina do Triangulo Mineiro, Uberaba, MG, Brazil
    Lancet Infect Dis 1:92-100. 2001
    ....
  5. ncbi Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis)
    Jose A Castro
    Centro de Investigaciones Toxicológicas CEITOX CITEFA CONICET, J B de La Salle 4397, Villa Martelli, Pcia de Buenos Aires 1603, Argentina
    Hum Exp Toxicol 25:471-9. 2006
    ..Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved...
  6. pmc State of the art in African trypanosome drug discovery
    Robert T Jacobs
    SCYNEXIS, Inc, Research Triangle Park, North Carolina 27709 2878, USA
    Curr Top Med Chem 11:1255-74. 2011
    ..This dire situation underscores the need for continued effort to identify new chemical agents for the treatment of HAT...
  7. pmc Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population
    Ana Maria Mejía
    Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, University of London, United Kingdom
    J Infect Dis 206:220-8. 2012
    ..They also demonstrate that T. cruzi has a propensity to undergo genetic changes that can lead to drug resistance, a finding that has implications for future therapeutic strategies...
  8. ncbi Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease
    L S Filardi
    Centro de Pesquisas Rene Rachou, FIOCRUZ, Belo Horizonte, Brazil
    Trans R Soc Trop Med Hyg 81:755-9. 1987
    ..Most of the 47 studied strains were either sensitive or resistant to both compounds, an intriguing finding considering that nifurtimox and benznidazole apparently have different mechanisms of action against T. cruzi...
  9. ncbi Pathogenesis of chronic Chagas heart disease
    Jose Antonio Marin-Neto
    Cardiology Division, Department of Internal Medicine, Medical School of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
    Circulation 115:1109-23. 2007
    ..Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction...
  10. ncbi The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease
    Najib M El-Sayed
    Department of Parasite Genomics, Institute for Genomic Research, Rockville, MD 20850, USA
    Science 309:409-15. 2005
    ....
  11. ncbi Tolerance and safety of nifurtimox in patients with chronic chagas disease
    Yves Jackson
    Divisionof Primary Care Medicine, Department of Community Medicine and Primary Care, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
    Clin Infect Dis 51:e69-75. 2010
    ..We aimed to evaluate nifurtimox tolerance and safety in a cohort of Trypanosoma cruzi-infected adult patients in a country of nonendemicity...
  12. pmc Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story
    Nicola Baker
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Trends Parasitol 29:110-8. 2013
    ..Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites...
  13. ncbi Sterol 14-demethylase inhibitors for Trypanosoma cruzi infections
    Frederick S Buckner
    Department of Medicine, University of Washington, Seattle, Washington, USA
    Adv Exp Med Biol 625:61-80. 2008
    ..In light of the near absence of adequate therapeutics for curing patients with chronic Chagas disease, additional effort to develop better drugs needs to be a priority...
  14. pmc A molecular mechanism for eflornithine resistance in African trypanosomes
    Isabel M Vincent
    University of Glasgow, Glasgow, UK
    PLoS Pathog 6:e1001204. 2010
    ..The loss of this transporter will be easily identified in the field using a simple PCR test, enabling more appropriate chemotherapy to be administered...
  15. pmc Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites
    Belinda S Hall
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    J Biol Chem 286:13088-95. 2011
    ..These experiments indicate that the basis for the selectivity of nifurtimox against T. brucei lies in the expression of a parasite-encoded type I nitroreductase...
  16. pmc Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom
    Antimicrob Agents Chemother 56:115-23. 2012
    ....
  17. pmc A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes
    Shane R Wilkinson
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Proc Natl Acad Sci U S A 105:5022-7. 2008
    ..This potential for drug resistance by a simple mechanism has important implications, because nifurtimox is currently undergoing phase III clinical trials against African trypanosomiasis...
  18. ncbi Chronic phase of Chagas disease: why should it be treated? A comprehensive review
    José Rodrigues Coura
    Laboratório de Doenças Parasitárias, Instituto Oswaldo Cruz FIOCRUZ, Rio de Janeiro, RJ, Brasil
    Mem Inst Oswaldo Cruz 106:641-5. 2011
    ....
  19. ncbi The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease
    J Antonio Marin-Neto
    Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brasil
    Mem Inst Oswaldo Cruz 104:319-24. 2009
    ..The full-scale study determines whether antitrypanosomal therapy with benznidazole reduces mortality and other major cardiovascular clinical outcomes in patients with chronic Chagas heart disease...
  20. pmc The trypanocide diminazene aceturate is accumulated predominantly through the TbAT1 purine transporter: additional insights on diamidine resistance in african trypanosomes
    Harry P de Koning
    Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom
    Antimicrob Agents Chemother 48:1515-9. 2004
    ..We conclude that TbAT1 mediates [(3)H]diminazene transport almost exclusively and that this explains the observed diminazene resistance phenotypes of TbAT1-null mutants and field isolates...
  21. pmc Human African trypanosomiasis of the CNS: current issues and challenges
    Peter G E Kennedy
    Department of Neurology, Division of Clinical Neurosciences, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland, United Kingdom
    J Clin Invest 113:496-504. 2004
    ..This review discusses the issues of diagnosis and staging of CNS disease, its neuropathogenesis, and the possibility of new therapies for treating late-stage disease...
  22. ncbi Loss of the high-affinity pentamidine transporter is responsible for high levels of cross-resistance between arsenical and diamidine drugs in African trypanosomes
    Daniel J Bridges
    Institute of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, United Kingdom
    Mol Pharmacol 71:1098-108. 2007
    ..It seems therefore that selection for resistance to either pentamidine or arsenical drugs can result in a similar phenotype of reduced drug accumulation, explaining the occurrence of cross-resistance...
  23. ncbi Efficacy of 10-day melarsoprol schedule 2 years after treatment for late-stage gambiense sleeping sickness
    C Schmid
    Swiss Tropical Institute, 4002 Basel, Switzerland
    Lancet 364:789-90. 2004
    ..After 2 years, 23 (5%) relapsing patients were reported, 11 (5%) in the standard treatment group and 12 (6%) in the new group. The results at the 2-year follow-up support and strengthen our previous findings...
  24. ncbi Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial
    Rodolfo Viotti
    Hospital Interzonal General de Agudos Eva Perón and Instituto Nacional de Parasitología Dr Mario Fatala Chaben, Buenos Aires, Argentina
    Ann Intern Med 144:724-34. 2006
    ..Benznidazole is effective for treating acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain...
  25. pmc New treatment option for second-stage African sleeping sickness: in vitro and in vivo efficacy of aza analogs of DB289
    Tanja Wenzler
    Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland
    Antimicrob Agents Chemother 53:4185-92. 2009
    ..In conclusion, DB868 with oral and DB829 with parenteral application are potential candidates for further development of a second-stage African sleeping sickness drug...
  26. ncbi Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial
    Gerardo Priotto
    Epicentre, Paris, France
    Lancet 374:56-64. 2009
    ..We assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the standard eflornithine regimen...
  27. ncbi Drug toxicity and cost as barriers to community participation in HAT control in the Democratic Republic of Congo
    J Robays
    Institute of Tropical Medicine, Epidemiology and Disease Control Unit, Antwerp, Belgium
    Trop Med Int Health 12:290-8. 2007
    ..The objectives of this survey were to explore community perception of HAT, to assess acceptability of control activities and to identify barriers amenable to intervention...
  28. ncbi The phenomenon of treatment failures in Human African Trypanosomiasis
    R Brun
    Swiss Tropical Institute, Basel, Switzerland
    Trop Med Int Health 6:906-14. 2001
    ..In conclusion, a combination of factors rather than a single one may be responsible for the phenomenon of melarsoprol treatment failures in T. b. gambiense patients...
  29. pmc Cross-resistance to nitro drugs and implications for treatment of human African trypanosomiasis
    Antoaneta Y Sokolova
    Division of Biological Chemistry and Drug Discovery, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Antimicrob Agents Chemother 54:2893-900. 2010
    ..This reciprocal cross-resistance has important implications for the therapeutic use of nifurtimox in a clinical setting and highlights a potential danger in the use of fexinidazole as a monotherapy...
  30. pmc Dissecting the essentiality of the bifunctional trypanothione synthetase-amidase in Trypanosoma brucei using chemical and genetic methods
    Susan Wyllie
    Division of Biological Chemistry and Drug Discovery, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK
    Mol Microbiol 74:529-40. 2009
    ..The synthetase function of TRYS is thus unequivocally validated as a drug target by both chemical and genetic methods...
  31. ncbi Chemotherapy against human African trypanosomiasis: is there a road to success?
    Christian Burri
    Swiss Tropical and Public Health Institute, Department of Medicines Research, Basel, Switzerland
    Parasitology 137:1987-94. 2010
    ..This review summarizes the key information about the existing drugs and gives a comprehensive summary about the recent and currently ongoing efforts towards new drugs...
  32. ncbi Trypanosoma brucei: a survey of pyrimidine transport activities
    Simon Gudin
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Biomedical Research Center, Glasgow G12 8TA, UK
    Exp Parasitol 114:118-25. 2006
    ..Pyrimidine antimetabolites were tested as potential trypanocidal agents and only 5-fluorouracil was found to be effective...
  33. pmc Trypanocidal activity of aziridinyl nitrobenzamide prodrugs
    Chris Bot
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Antimicrob Agents Chemother 54:4246-52. 2010
    The trypanocidal agents nifurtimox and benznidazole both function as prodrugs and must undergo enzyme-mediated activation, a reaction catalyzed by type I nitroreductase (NTR)...
  34. ncbi Lepadins D-F: antiplasmodial and antitrypanosomal decahydroquinoline derivatives from the tropical marine tunicate Didemnum sp
    Anthony D Wright
    Institute for Pharmaceutical Biology, Technical University of Braunschweig, Mendelssohnstrasse 1, 38106 Braunschweig, Germany
    J Med Chem 45:3067-72. 2002
    ..These isolates may well serve as lead structures for the development of new antimalarial drugs...
  35. pmc Multiple genetic mechanisms lead to loss of functional TbAT1 expression in drug-resistant trypanosomes
    Mhairi L Stewart
    Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, United Kingdom
    Eukaryot Cell 9:336-43. 2010
    ..b. brucei mutant, although at a greatly reduced capacity compared to that of the wild type, indicating that an additional adenine-inhibitable adenosine permease, distinct from P2, is present in these cells...
  36. pmc In vitro and in vivo studies of the antiparasitic activity of sterol 14α-demethylase (CYP51) inhibitor VNI against drug-resistant strains of Trypanosoma cruzi
    Maria de Nazaré Correia Soeiro
    Laboratório de Biologia Celular do IOC, Fundacao Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
    Antimicrob Agents Chemother 57:4151-63. 2013
    ..Thus, these preliminary studies confirm VNI as a very promising trypanocidal drug candidate for Chagas disease therapy. ..
  37. ncbi Drug resistance in human African trypanosomiasis
    Michael P Barrett
    Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland
    Future Microbiol 6:1037-47. 2011
    ....
  38. ncbi Antitrypanosomal cyclic polyketide peroxides from the Australian marine sponge Plakortis sp
    Yunjiang Feng
    Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia
    J Nat Prod 73:716-9. 2010
    ..11,12-Didehydro-13-oxo-plakortide Q (1) is the most active peroxide isolated so far against T. b. brucei, and it indicates the potential therapeutic value of this class of compounds...
  39. ncbi Convolutamines I and J, antitrypanosomal alkaloids from the bryozoan Amathia tortusa
    Rohan A Davis
    Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia
    Bioorg Med Chem 19:6615-9. 2011
    ..Compound 1 was shown to exhibit cytotoxicity against HEK293 with an IC(50) of 22.0 μM whilst 2 was inactive at 41.0 μM...
  40. pmc Targeting Trypanosoma cruzi sterol 14α-demethylase (CYP51)
    Galina I Lepesheva
    Department of Biochemistry School of Medicine, Vanderbilt University, Nashville, Tennessee, USA
    Adv Parasitol 75:65-87. 2011
    ..We believe our studies open wide opportunities for rational design of novel, pathogen-specific and therefore more potent and efficient anti-trypanosomal drugs...
  41. ncbi Manadoperoxides, a new class of potent antitrypanosomal agents of marine origin
    Giuseppina Chianese
    Dipartimento di Chimica delle Sostanze Naturali, Universita di Napoli Federico II, Napoli, Italy
    Org Biomol Chem 10:7197-207. 2012
    ..This information can be valuable to guide the design of optimized antitrypanosomal agents based on the dioxane scaffold...
  42. pmc Discovery of novel orally bioavailable oxaborole 6-carboxamides that demonstrate cure in a murine model of late-stage central nervous system african trypanosomiasis
    Bakela Nare
    SCYNEXIS, Inc, Research Triangle Park, North Carolina 27713, USA
    Antimicrob Agents Chemother 54:4379-88. 2010
    ..These properties strongly suggest that these novel chemical entities are suitable leads for the development of new and effective orally administered treatments for human African trypanosomiasis...
  43. ncbi Risk factors for treatment failure after melarsoprol for Trypanosoma brucei gambiense trypanosomiasis in Uganda
    D Legros
    Epicentre, Kampala, Uganda
    Trans R Soc Trop Med Hyg 93:439-42. 1999
    ..The study emphasizes the need for second-line drugs to treat patients that have already received one or several full course(s) of melarsoprol...
  44. pmc The distribution of nifurtimox across the healthy and trypanosome-infected murine blood-brain and blood-cerebrospinal fluid barriers
    Sinthujah Jeganathan
    Pharmaceutical Sciences Research Division, King s College London, London, United Kingdom
    J Pharmacol Exp Ther 336:506-15. 2011
    ..Consequently, CNS efficacy may be improved with nifurtimox-pentamidine combinations, but over time may be reduced when nifurtimox is combined with eflornithine, suramin, or melarsoprol...
  45. ncbi Trypanocidal action of eupomatenoid-5 is related to mitochondrion dysfunction and oxidative damage in Trypanosoma cruzi
    Karin Juliane Pelizzaro-Rocha
    Programa de Pós Graduação em Microbiologia, Universidade Estadual de Londrina, Londrina, PR, Brazil
    Microbes Infect 13:1018-24. 2011
    ..Thus, the trypanocidal action of eupomatenoid-5 may be associated with mitochondrial dysfunction and oxidative damage, which can trigger destructive effects on biological molecules of T. cruzi, leading to parasite death...
  46. pmc Investigation of trypanothione reductase as a drug target in Trypanosoma brucei
    Daniel Spinks
    Drug Discovery Unit, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH, UK
    ChemMedChem 4:2060-9. 2009
    ..Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme and growth of the parasite. The challenges of inhibiting TryR with druglike molecules is discussed...
  47. ncbi Trypanosoma cruzi: activity of heterocyclic cationic molecules in vitro
    Michele Gabriele de Oliveira Pacheco
    Lab Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, M N C Soeiro, Rio de Janeiro, Brazil
    Exp Parasitol 123:73-80. 2009
    ..cruzi infection...
  48. pmc In vitro and in vivo studies of the trypanocidal activity of a diarylthiophene diamidine against Trypanosoma cruzi
    Cristiane França Da Silva
    Lab Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
    Antimicrob Agents Chemother 52:3307-14. 2008
    ..cruzi infection. These results support further investigation of diamidines and related compounds as potential agents against Chagas' disease...
  49. ncbi Trypanosoma cruzi targets for new chemotherapeutic approaches
    Maria Nazaré C Soeiro
    Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Laboratorio de Biologia Celular, Avenue Brazil 4365, Manguinhos, 21045 900, Rio de Janeiro, RJ, Brazil
    Expert Opin Ther Targets 13:105-21. 2009
    ....
  50. ncbi Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro"
    C F Silva
    Lab Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
    Biochem Pharmacol 73:1939-46. 2007
    ..Our results show the activity of reversed diamidines against T. cruzi and suggested that the compounds merit in vivo studies...
  51. ncbi Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice
    Thierry Lang
    Unité d Immunophysiologie et Parasitisme Intracellulaire, Departement de Parasitologie, Institut Pasteur, rue 25 du Dr Roux, 75724 Paris Cedex 15, France
    Cell Microbiol 7:383-92. 2005
    ..In short, this luciferase imaging study is useful to monitor the efficacy of anti-leishmanial drugs on live cell culture and to trace leishmanial infection in animal models...
  52. ncbi Mode of action of nifurtimox and N-oxide-containing heterocycles against Trypanosoma cruzi: is oxidative stress involved?
    Mariana Boiani
    Laboratorio de Química Orgánica, Facultad de Ciencias Facultad de Química, Universidad de la Republica, Montevideo, Uruguay
    Biochem Pharmacol 79:1736-45. 2010
    ..The indazole derivative raised intracellular oxidants production, but it was the least effective as anti-T. cruzi...
  53. pmc Changes in Trypanosoma cruzi-specific immune responses after treatment: surrogate markers of treatment efficacy
    Susana A Laucella
    Instituto Nacional de Parasitologia Dr Mario Fatala Chaben, Buenos Aires, San Martin, Provincia de Buenos Aires, Argentina
    Clin Infect Dis 49:1675-84. 2009
    ..The major limitation in developing and evaluating potential new drugs for their efficacy is the lack of reliable tests to assess parasite burden and elimination...
  54. ncbi Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution
    Diana L Fabbro
    Centro de Investigaciones sobre Endemias Nacionales, Facultad de Bioquimica y Ciencias Biologicas, Universidad Nacional del Litoral, Santa Fe, Argentina
    Rev Soc Bras Med Trop 40:1-10. 2007
    ..05). Treatment caused deparasitation in at least 37% of the chronically infected adults and a protective effect on their clinical evolution...
  55. ncbi Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities
    Rodolfo Viotti
    Servicio de Cardiologia, Hospital Eva Perón, San Martín José Hernández 3440, Villa Ballester 1653, Buenos Aires, Argentina
    Expert Rev Anti Infect Ther 7:157-63. 2009
    ....
  56. ncbi A nucleoside transporter from Trypanosoma brucei involved in drug resistance
    P Maser
    Swiss Tropical Institute, CH 4002 Basel, Switzerland Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    Science 285:242-4. 1999
    ..Drug-resistant trypanosomes harbor a defective TbAT1 variant. The molecular identification of the entry route of trypanocides opens the way to approaches for diagnosis and treatment of drug-resistant sleeping sickness...
  57. ncbi Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole
    Gustavo Benaim
    Laboratorio Química Biológica and Laboratorio de Permeabilidad Iónica, Instituto Venezolano de Investigaciones Cientificas, Apartado 21927, Caracas 1020A, Venezuela
    J Med Chem 49:892-9. 2006
    ..cruzi and open up the possibility of novel, combination therapy approaches to the treatment of Chagas' disease using currently approved drugs...
  58. ncbi Drug-resistance of Trypanosoma b. rhodesiense isolates from Tanzania
    S N Kibona
    National Institute for Medical Research, Tabora, Tanzania
    Trop Med Int Health 11:144-55. 2006
    ..To determine the drug resistance of Trypanosoma brucei rhodesiense strains isolated from sleeping sickness patients in Tanzania...
  59. ncbi Is there safety in numbers? The effect of cattle herding on biting risk from tsetse flies
    S J Torr
    Natural Resources Institute, University of Greenwich, Greenwich, U K
    Med Vet Entomol 21:301-11. 2007
    ....
  60. ncbi Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II)
    Caecilia Schmid
    Swiss Tropical Institute, Basel
    J Infect Dis 191:1922-31. 2005
    ..A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study...
  61. pmc High failure rates of melarsoprol for sleeping sickness, Democratic Republic of Congo
    Jo Robays
    Institute of Tropical Medicine, Antwerp, Belgium
    Emerg Infect Dis 14:966-7. 2008
    ..5%. This rate increased over the 3 years. Relapse rates were highest in the central part of the province...
  62. ncbi In vitro anti-trypanosomal activity of elatol isolated from red seaweed Laurencia dendroidea
    P Veiga-Santos
    Programa de Pós Graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B 08, Universidade Estadual de Maringa, Av Colombo 5790, CEP 87020 900 Maringa, Parana, Brazil
    Parasitology 137:1661-70. 2010
    ..This is the first report of the anti-trypanosomal effect of the sesquiterpene elatol...
  63. pmc Differential gene expression in benznidazole-resistant Trypanosoma cruzi parasites
    Diana Villarreal
    Génétique et Evolution des Maladies Infectieuses G E M I, UMR 2724 CNRS IRD, UR 165 IRD, Centre de Recherche IRD, 911 Avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France
    Antimicrob Agents Chemother 49:2701-9. 2005
    ..No significant association was found between phylogenetic clustering and benznidazole susceptibility. Benznidazole resistance may involve several mechanisms, depending on the level of drug exposure...
  64. ncbi Molecular characterization of cytosolic and mitochondrial tryparedoxin peroxidase in Trypanosoma cruzi populations susceptible and resistant to benznidazole
    Fernanda B Nogueira
    Laboratório de Parasitologia Celular e Molecular, Centro de Pesquisas Rene Rachou, FIOCRUZ, Av Augusto de Lima 1715, 30190 002 Belo Horizonte, MG, Brazil
    Parasitol Res 104:835-44. 2009
    ..5-fold greater expression in the 17 LER population than 17 WTS. Our findings demonstrate increased expression of the cytosolic and mitochondrial TcTXNPx in the T. cruzi population with in-vitro-induced resistance to benznidazole...
  65. pmc Antiproliferative effects and mechanism of action of SCH 56592 against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies
    J A Urbina
    Laboratorio de Quimica Biologica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela
    Antimicrob Agents Chemother 42:1771-7. 1998
    ..The results indicate that SCH 56592 is the most powerful sterol biosynthesis inhibitor ever tested against T. cruzi and may be useful in the treatment of human Chagas' disease...
  66. pmc Human African trypanosomiasis: pharmacological re-engagement with a neglected disease
    M P Barrett
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, The Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK
    Br J Pharmacol 152:1155-71. 2007
    ..Finally we report on new initiatives that might allow progress to be made in developing new and satisfactory drugs for this terrible disease...
  67. ncbi Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas' disease, and leishmaniasis
    O Heby
    Department of Molecular Biology, Umea University, Umea, Sweden
    Amino Acids 33:359-66. 2007
    ..By taking advantage of the differences in enzyme structure between parasite and host, it should be possible to design new drugs that can selectively kill the parasites...
  68. ncbi Trypanosome alternative oxidase: from molecule to function
    Minu Chaudhuri
    Division of Microbial Pathogenesis and Immune Response, Department of Biomedical Sciences, Meharry Medical College, Nashville, TN 37208, USA
    Trends Parasitol 22:484-91. 2006
    ..Alternative oxidases similar to TAO have been found in a wide variety of organisms but not in mammals, thus rendering TAO an important chemotherapeutic target for African trypanosomiasis...
  69. ncbi Side effects of benznidazole treatment in a cohort of patients with Chagas disease in non-endemic country
    B Carrilero
    Unidad Regional de Medicina Tropical, Servicio de Microbiologia, Hospital Universitario Virgen de la Arrixaca, Carretera Madrid Cartagena, El Palmar Murcia, Spain
    Rev Esp Quimioter 24:123-6. 2011
    ..1% (34 of 373). Surprisingly, three cases of migratory arthritis were observed. Patients treated with benznidazole must be followed up so that the long term incidence of side effects can be studied...
  70. pmc Novel African trypanocidal agents: membrane rigidifying peptides
    John M Harrington
    Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America
    PLoS ONE 7:e44384. 2012
    ..Additionally, the peptides we have described may be valuable tools for probing the biosynthetic machinery responsible for the unique composition and characteristics of African trypanosome plasma membranes...
  71. ncbi Characterisation of cloned lines of Trypanosoma brucei expressing stable resistance to MelCy and suramin
    A G Scott
    Parasitology Laboratory, University of Glasgow, UK
    Acta Trop 60:251-62. 1996
    ..We propose that this difference between the in vivo and in vitro results for melB may indicate that an alteration in a surface adenosine transporter responsible for reduced melCy uptake was bypassed by melB over 24 hours in vitro...
  72. ncbi Ghibe river basin in Ethiopia: present situation of trypanocidal drug resistance in Trypanosoma congolense using tests in mice and PCR-RFLP
    Y Moti
    Department of Microbiology and Veterinary Public Health, Jimma University, College of Agriculture and Veterinary Medicine, P O Box 307, Jimma, Ethiopia
    Vet Parasitol 189:197-203. 2012
    ..001). Relapsing time after treatment with DA 10mg/kg B.W. or ISM 1mg/kg B.W. was also significantly longer than the prepatent period of the control group. The situation of drug resistance in the Ghibe valley is further discussed...
  73. ncbi Analogues of fenarimol are potent inhibitors of Trypanosoma cruzi and are efficacious in a murine model of Chagas disease
    Martine Keenan
    Epichem Pty Ltd, South Street, Murdoch, WA 6150, Australia
    J Med Chem 55:4189-204. 2012
    ..Chemical and biological studies undertaken in the development of the fenarimol series toward the goal of delivering a new drug candidate for Chagas disease are reported...
  74. ncbi Novel markers for treatment outcome in late-stage Trypanosoma brucei gambiense trypanosomiasis
    Veerle Lejon
    Department of Parasitology, Institute of Tropical Medicine, Nationalestraat 155, B 2000 Antwerpen, Belgium
    Clin Infect Dis 47:15-22. 2008
    ..The accuracy of biological markers for prediction of treatment outcome of HAT caused by Trypanosoma brucei gambiense was assessed...
  75. ncbi Effects of inhibitors of Delta24(25)-sterol methyl transferase on the ultrastructure of epimastigotes of Trypanosoma cruzi
    Marina V Braga
    Laboratorio de Ultraestrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS Bloco G, Ilha do Fundao, 21949 900, Rio de Janeiro RJ, Brasil
    Microsc Microanal 11:506-15. 2005
    ..Our results show that these drugs are potent in vitro inhibitors of growth of T. cruzi...
  76. ncbi Propidium iodide-based methods for monitoring drug action in the kinetoplastidae: comparison with the Alamar Blue assay
    Matthew K Gould
    Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, 120 University Place, Glasgow G128TA, UK
    Anal Biochem 382:87-93. 2008
    ..The EC(50) values were highly similar to those obtained with the standard Alamar Blue assay. The procedure lends itself readily to applications in drug development or resistance monitoring...
  77. pmc Design, synthesis and biological evaluation of Trypanosoma brucei trypanothione synthetase inhibitors
    Daniel Spinks
    Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, UK
    ChemMedChem 7:95-106. 2012
    ..Cellular studies on these inhibitors confirmed on-target activity, and the compounds have proven to be very useful tools for further study of the trypanothione pathway in kinetoplastids...
  78. pmc Assessing the essentiality of Leishmania donovani nitroreductase and its role in nitro drug activation
    Susan Wyllie
    Division of Biological Chemistry and Drug Discovery, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
    Antimicrob Agents Chemother 57:901-6. 2013
    ..donovani promastigotes, combined with the limited resistance shown by NTR single knockout cells, suggests that the potential for the spread of NTR-based resistance to fexinidazole may be limited...
  79. pmc Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi
    Katharine R Watts
    Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, USA
    Bioorg Med Chem 18:2566-74. 2010
    ..A preliminary activity pattern is described and analyzed...
  80. pmc Activity of megazol, a trypanocidal nitroimidazole, is associated with DNA damage
    Bertin Enanga
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
    Antimicrob Agents Chemother 47:3368-70. 2003
    ..Parasites resistant to megazol were selected and showed modest cross-resistance to other trypanocides, although neither drug efflux nor changes to intracellular thiols correlated with resistance...
  81. ncbi Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease
    Margoth Moreno
    Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, SP, Brasil
    Mem Inst Oswaldo Cruz 105:918-24. 2010
    ..A two-fold increase in BZ resistance in the post-treatment isolates of two patients was verified. Based on the profile of nine microsatellite loci, sub-population selection in non-cured patients was ruled out...
  82. ncbi Suramin: clinical uses and structure-activity relationships
    Ross P McGeary
    School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
    Mini Rev Med Chem 8:1384-94. 2008
    ..Suramin has also been extensively trialed recently to treat a number of other diseases, including many cancers. Here, we examine its modes of action and discuss its structure-activity relationships...
  83. ncbi Probing enzymes late in the trypanosomal glycosylphosphatidylinositol biosynthetic pathway with synthetic glycosylphosphatidylinositol analogues
    Michael D Urbaniak
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    ACS Chem Biol 3:625-34. 2008
    ....
  84. ncbi Trypanocidal drugs: mechanisms, resistance and new targets
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK
    Expert Rev Mol Med 11:e31. 2009
    ..being facilitated by new research networks that involve academic and biotechnology/pharmaceutical organisations, supported by public-private partnerships, and are bringing a new dynamism and purpose to the search for trypanocidal agents.
  85. pmc Antitumor quinol PMX464 is a cytocidal anti-trypanosomal inhibitor targeting trypanothione metabolism
    Janine König
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 286:8523-33. 2011
    ..Thus, the quinol pharmacophore represents a novel lead structure for the development of a new drug against African sleeping sickness...
  86. ncbi Further probing of the substrate specificities and inhibition of enzymes involved at an early stage of glycosylphosphatidylinositol (GPI) biosynthesis
    Arthur Crossman
    School of Life Sciences Chemistry, Carnelley Building, University of Dundee, Dundee DD1 4HN, UK
    Carbohydr Res 337:2049-59. 2002
    ..A brief summary of the biological evaluation of the various analogues is provided...
  87. ncbi Screening of some Tanzanian medicinal plants for their trypanocidal and cytotoxic activities
    Endalkachew Nibret
    Institut für Pharmazie und molekulare Biotechnologie, Universitat Heidelberg, Heidelberg, Germany
    Phytother Res 24:945-7. 2010
    ....
  88. pmc Tolerance of benznidazole in treatment of Chagas' disease in adults
    María Jesús Pinazo
    Tropical Diseases Section, Barcelona Centre for International Health Research, Hospital Clinic, Villarroel 170, Barcelona, Spain
    Antimicrob Agents Chemother 54:4896-9. 2010
    ..This study describes the profile of side effects of benznidazole in a cohort of Trypanosoma cruzi-infected patients in a European country...
  89. ncbi Genotypic and phenotypic characterization of Trypanosoma brucei gambiense isolates from Ibba, South Sudan, an area of high melarsoprol treatment failure rate
    Naomi Maina
    Trypanosomiasis Research Institute TRC, PO Box 362, Kikuyu, Kenya
    Acta Trop 104:84-90. 2007
    ..These findings indicate that factors other than drug resistance contribute to melarsoprol treatment failures...
  90. ncbi Increased expression of iron-containing superoxide dismutase-A (TcFeSOD-A) enzyme in Trypanosoma cruzi population with in vitro-induced resistance to benznidazole
    Fernanda B Nogueira
    Laboratório de Parasitologia Celular e Molecular, Centro de Pesquisas Rene Rachou, FIOCRUZ, Av Augusto de Lima 1715, 30190 002 Belo Horizonte, MG, Brazil
    Acta Trop 100:119-32. 2006
    ..cruzi samples revealed a correlation between expression and activity. Our findings show an increased expression of the TcFeSOD-A enzyme in the T. cruzi population with in vitro-induced resistance to benznidazole...
  91. ncbi In vitro and in vivo activities of ravuconazole on Trypanosoma cruzi, the causative agent of Chagas disease
    Julio A Urbina
    Laboratorio de Quimica Biologica, Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Apartado 21827, Caracas 1020A, Venezuela
    Int J Antimicrob Agents 21:27-38. 2003
    ..However, these results do not necessarily rule out the potential utility of ravuconazole in the treatment of human T. cruzi infections...
  92. ncbi [Human african trypanosomiasis: A history of its therapies and their failures.]
    G Ollivier
    Epicentre, Paris, France
    Trop Med Int Health 6:855-63. 2001
    ..This paper gives an overview of the treatment of Human African Trypanosomiasis from the early 20th century until today...
  93. ncbi Comparison of operational criteria for treatment outcome in gambiense human African trypanosomiasis
    D Mumba Ngoyi
    Institut National de Recherche Biomédicale, Avenue de la Démocratie, Kinshasa, Democratic Republic of the Congo
    Trop Med Int Health 14:438-44. 2009
    ....
  94. ncbi Benznidazole biotransformation in rat heart microsomal fraction without observable ultrastructural alterations: comparison to Nifurtimox-induced cardiac effects
    María Montalto de Mecca
    Centro de Investigaciones Toxicológicas CEITOX CITEFA CONICET, Villa Martelli, Buenos Aires, Argentina
    Mem Inst Oswaldo Cruz 103:549-53. 2008
    ..In conclusion, when these drugs are used in chagasic patients, Bz may pose a lesser risk to heart function than Nfx when any cardiopathy is present...
  95. pmc 2,N6-disubstituted adenosine analogs with antitrypanosomal and antimalarial activities
    Boris Rodenko
    van t Hoff Institute for Molecular Sciences, Universiteit van Amsterdam, The Netherlands
    Antimicrob Agents Chemother 51:3796-802. 2007
    ..b. brucei strain lacking the P2 nucleoside transporter as they were against the parental strain. As the analogs were not toxic to human cell lines, the purine analogs are likely to act on a trypanosome-specific target...
  96. ncbi Drug target validation of the trypanothione pathway enzymes through metabolic modelling
    Viridiana Olín-Sandoval
    Departamento de Bioquimica, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico Distrito Federal, Mexico
    FEBS J 279:1811-33. 2012
    ..In contrast, use of highly potent and specific inhibitors for TryR and the antioxidant machinery is necessary to affect the antioxidant capabilities of the parasites...
  97. ncbi Preventing and containing trypanocide resistance in the cotton zone of West Africa
    P H Clausen
    Institute for Parasitology and Tropical Veterinary Medicine, Freie Universitaet Berlin, Berlin, Germany
    Transbound Emerg Dis 57:28-32. 2010
    ..Engagement was initiated with actors involved in the problem of resistance and for its solution, including manufacturers, sellers and users of drugs, regulators and extension providers...
  98. ncbi Synthesis, inhibition potency, binding mode, and antiprotozoal activities of fluorescent inhibitors of trypanothione reductase based on mepacrine-conjugated diaryl sulfide scaffolds
    Christian Eberle
    Laboratorium fur Organische Chemie, ETH Zurich, Honggerberg, HCI, 8093 Zurich, Switzerland
    ChemMedChem 4:2034-44. 2009
    ..The inhibitors exhibit strong fluorescence due to their aminoacridine moiety. This feature allows visualization of the drugs in the parasite where high accumulation was observed by fluorescence microscopy even after short exposure times...
  99. ncbi Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies
    Maria de Nazaré C Soeiro
    Laboratorio de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brasil
    Mem Inst Oswaldo Cruz 104:301-10. 2009
    ..cruzi efficacy...
  100. pmc Two approaches to discovering and developing new drugs for Chagas disease
    J H McKerrow
    Sandler Center at Mission Bay, University of California, San Francisco, CA 94158 2330, USA
    Mem Inst Oswaldo Cruz 104:263-9. 2009
    ..It is optimized for robotic liquid handling and has been validated through a screen of a library of FDA-approved drugs identifying 65 hits...
  101. pmc Exploiting the drug-activating properties of a novel trypanosomal nitroreductase
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom
    Antimicrob Agents Chemother 54:1193-9. 2010
    ..We conclude that halogenated nitrobenzylphosphoramide mustards represent a novel class of antitrypanosomal agents, and their efficacy validates the strategy of specifically targeting NTR activity to develop new therapeutics...

Research Grants34

  1. Functions of nuclear non-canonical poly(A) polymerases in Trypanosomes
    Ruslan Aphasizhev; Fiscal Year: 2010
    ..Targeting essential parasite-specific enzymes, such as nuclear non-canonical poly(A) polymerase introduced in our application, is a promising approach toward creating a new generation of trypanocides. ..
  2. Global gene expression analysis of Trypanosoma cruzi under hyperosmotic stress
    Roberto Docampo; Fiscal Year: 2012
    ..from the response of mammalian cells to similar stresses and their study may lead to the discovery of new targets for trypanocidal agents. This work is designed to investigate the roles and significance of these pathways in T. cruzi.
  3. Structures and Functions of RNA Editing TUTases
    RUSLAN AFASIZHEV; Fiscal Year: 2013
    ..Targeting essential parasite-specific enzymes, such as mitochondrial RNA editing terminal uridylyl transferases (TUTases), is a promising approach toward a new generation of trypanocides. ..
  4. Mitochondrial poly(A) Polymerases of Trypanosomes
    Ruslan Aphasizhev; Fiscal Year: 2009
    ..However, a detailed molecular analysis of the polyadenylation process is required for validation of this enzyme as a drug target. ..
  5. CATIONIC TRYPANOCIDES: POLYAMINES AND LETHALITY
    SEYMOUR HUTNER; Fiscal Year: 1980
    ..e., no excess of metabolites, for two isolates of Crithidia growing at 37 C, replacing the serum in the suspension vehicle for T. brucei cells, and developing means of ensuring sustained release of drugs in the mouse model. ..
  6. POLYAMINES IN TRYPANOSOMES--FUNCTION AND METABOLISM
    Cyrus Bacchi; Fiscal Year: 1980
    ..The effect of exogenously added polyamines on the curative effect of the drug is also determined, using subcurative (but lifeprolonging) drug doses and nontoxic polyamine levels. ..
  7. TRYPANOTHIONE--A TARGET FOR DRUG DESIGN IN TRYPANOSOMES
    B HENDERSON GRAEME; Fiscal Year: 1990
    ..Consequently, this aspect of parasite biochemistry represents an important new area for pharmacological intervention...
  8. Sterol Biosynthesis in Trypanosomatid Parasites
    Frederick Buckner; Fiscal Year: 2004
    ..The drugs discovered in this research program will hopefully provide better future treatment for patients with these devastating diseases. ..
  9. High Throughput Assay for Screening Compounds(RMI)
    James McKerrow; Fiscal Year: 2005
    ..Computational and informatics capability is in place to acquire, store and cross-reference this data, and provide access to the scientific community through an open-source website. ..
  10. Water-Soluble and Metabolically Stable Calpain Inhibitors as Cardioprotectants
    ISAAC DONKOR; Fiscal Year: 2008
    ..Furthermore, the proposed studies will provide mechanistic insight into the mode of action of calpain inhibitors as cardioprotectants. ..
  11. Host Protein Degradation by Schistosome Parasites
    James McKerrow; Fiscal Year: 2007
    ..abstract_text> ..
  12. Targeting Cysteine Proteases: Antiparasitic Chemotherapy
    James McKerrow; Fiscal Year: 2008
    ..No Abstract Provided. ..
  13. Chemoprevention Potential of Calpain Inhibitors
    ISAAC DONKOR; Fiscal Year: 2007
    ..The proposal is significant and innovative because it seeks to investigate calpain as a pharmacological target for the discovery of a new class of chemoprevention agents. [unreadable] [unreadable] [unreadable]..
  14. Targeting Calpain for Novel Anticancer Agents
    ISAAC DONKOR; Fiscal Year: 2005
    ..Additionally, the compounds are useful biomedical tools for investigating the intracellular roles of Calpain due to their metabolic stability. The compounds are also potential anticancer agents. ..
  15. PROBING THE S' SUBSITES OF CALPAIN
    ISAAC DONKOR; Fiscal Year: 2002
    ..Selected potent and cell permeable inhibitors will be tested in the rat isolated heart ischemia model for cardioprotective effect. ..
  16. Conference on Drug Against Tropical Protozoan Parasites
    Michael Gelb; Fiscal Year: 2002
    ..We consider the poster sessions that occur throughout our meeting to be just as important as the collection of lecture presentations. ..
  17. Development of Assay for High Throughput Screen of Parasite Glucose Transporter
    Scott M Landfear; Fiscal Year: 2010
    ..Since glucose is an essential nutrient for these parasites, such compounds would kill the parasite and could act as novel drugs for treatment of the diseases they cause. ..
  18. CHAGAS DISEASE: AUTOIMMUNITY STEMS FROM PARASITE INVASION OF HOST GENOME
    Antonio Teixeira; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  19. Flavoenzymes in Pyrimidine Metabolism
    Bruce A Palfey; Fiscal Year: 2011
    ..Our studies of the rates of the chemical reactions will identify important parts of the proteins, how they move during reactions, how they speed the synthesis of products, and how these reactions might be blocked. ..
  20. MULTIPLEX ANALYSIS OF INBORN ERRORS OF METABOLISM
    Michael Gelb; Fiscal Year: 2001
    ..abstract_text> ..
  21. Transcription of protein-coding genes in Leishmania
    PETER JOHN MYLER; Fiscal Year: 2010
    ..In this proposal, we will test this hypothesis and build on our current work to further characterize the chromatin-modifying enzymes that are involved in transcription initiation. ..
  22. Simple, Selective Antimitotic Antiparasitic Agents
    Karl Werbovetz; Fiscal Year: 2007
    ..abstract_text> ..
  23. FOCUSED PARALLEL SYNTHESIS OF DICATION ANTIFUNGAL AGENTS
    Richard Tidwell; Fiscal Year: 2003
    ..abstract_text> ..
  24. BIOCHEMISTRY OF PROTEIN PRENYLATION
    Michael Gelb; Fiscal Year: 2002
    ....
  25. Telomere structure and function in Trypanosoma brucei
    GEORGE CROSS; Fiscal Year: 2005
    ..There are significant similarities between the telomeres of trypanosomes and humans, so trypanosomes would be a useful model in which to study events that are relevant to human aging and cancer. ..
  26. DEVELOPMENT OF GENETIC TOOLS FOR TRYPANOSOMA BRUCEI
    GEORGE CROSS; Fiscal Year: 2006
    ..abstract_text> ..
  27. AP13000 LCMS/MS System
    Richard Tidwell; Fiscal Year: 2002
    ..Drs. Hall and Kashuba will prioritize CPA CC use and Dr. Gary Pollack will prioritize use by School of Pharmacy scientists. The instrument will be housed in newly renovated space in the School of Pharmacy. ..
  28. MITOCHONDRIAL PROTEIN IMPORT IN AFRICAN TRYPANOSOMES
    Minu Chaudhuri; Fiscal Year: 2002
    ..Understanding of this developmental process will elucidate one of the major aspects of trypanosomal parasitism. This in turn will help us to design rational trypanocidal chemotherapeutic strategies. ..
  29. BIOCHEMICAL STUDIES OF 14 KDA PHOSPHOLIPASES A2
    Michael Gelb; Fiscal Year: 2006
    ..These studies will contribute to our fundamental understanding of how mammalian cells initiate the eicosanoid cascade. ..
  30. Human papillomavirus as a risk factor for HIV infection
    PETER CHIN HONG; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  31. Functional Characterization of Leishmania Transporters
    Scott M Landfear; Fiscal Year: 2010
    ..Overall, this proposal will provide a detailed biochemical and genetic dissection of glucose transporter function and the essential role of these permeases in the parasite life cycle. ..
  32. Topoisomerases: Target for Antitrypanosomal Therapy
    Theresa Shapiro; Fiscal Year: 2006
    ..Compounds that appear most promising will be evaluated in mice. These studies take a multi-faceted, rational, and tangible approach to the development of much-needed new anti-trypanosomal chemotherapy. ..