Reto Brun

Summary

Affiliation: University of Basel
Country: Switzerland

Publications

  1. pmc Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model
    Kirsten Gillingwater
    Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    PLoS ONE 6:e20836. 2011
  2. pmc In vitro interaction of artemisinin derivatives or the fully synthetic peroxidic anti-malarial OZ277 with thapsigargin in Plasmodium falciparum strains
    Oyindamola O Abiodun
    Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria
    Malar J 12:43. 2013
  3. pmc Anti-protozoal activity of aporphine and protoberberine alkaloids from Annickia kummeriae (Engl. & Diels) Setten & Maas (Annonaceae)
    Hamisi M Malebo
    Department of Traditional Medicine Research, National Institute for Medical Research, P O Box 9653, Dar es Salaam, Tanzania
    BMC Complement Altern Med 13:48. 2013
  4. doi request reprint Human African trypanosomiasis
    Reto Brun
    Department Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH 4002 Basel, Switzerland
    Infect Dis Clin North Am 26:261-73. 2012
  5. ncbi request reprint New developments in human African trypanosomiasis
    Reto Brun
    Swiss Tropical Institute, Parasite Chemotherapy, Basel, Switzerland
    Curr Opin Infect Dis 19:415-20. 2006
  6. doi request reprint Human African trypanosomiasis
    Reto Brun
    Swiss Tropical Institute, Basel, Switzerland
    Lancet 375:148-59. 2010
  7. ncbi request reprint The story of CGP 40 215: studies on its efficacy and pharmacokinetics in African green monkey infected with Trypanosoma brucei rhodesiense
    R Brun
    Swiss Tropical Institute, Basel, Switzerland
    Trop Med Int Health 6:362-8. 2001
  8. ncbi request reprint The phenomenon of treatment failures in Human African Trypanosomiasis
    R Brun
    Swiss Tropical Institute, Basel, Switzerland
    Trop Med Int Health 6:906-14. 2001
  9. doi request reprint In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi
    Kirsten Gillingwater
    Parasite Chemotherapy, Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, 4002 Basel, Switzerland
    Vet Parasitol 169:264-72. 2010
  10. pmc Pharmacokinetics, Trypanosoma brucei gambiense efficacy, and time of drug action of DB829, a preclinical candidate for treatment of second-stage human African trypanosomiasis
    Tanja Wenzler
    Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    Antimicrob Agents Chemother 57:5330-43. 2013

Detail Information

Publications96

  1. pmc Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model
    Kirsten Gillingwater
    Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    PLoS ONE 6:e20836. 2011
    ..In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection...
  2. pmc In vitro interaction of artemisinin derivatives or the fully synthetic peroxidic anti-malarial OZ277 with thapsigargin in Plasmodium falciparum strains
    Oyindamola O Abiodun
    Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria
    Malar J 12:43. 2013
    ..The latter compound is an adamantane-based peroxide and the first fully synthetic clinical candidate recently registered in India by Ranbaxy Laboratories Ltd. for anti-malarial combination therapy...
  3. pmc Anti-protozoal activity of aporphine and protoberberine alkaloids from Annickia kummeriae (Engl. & Diels) Setten & Maas (Annonaceae)
    Hamisi M Malebo
    Department of Traditional Medicine Research, National Institute for Medical Research, P O Box 9653, Dar es Salaam, Tanzania
    BMC Complement Altern Med 13:48. 2013
    ..Consequently, there is an urgent need for research aimed at the discovery and development of new effective and safe anti-plasmodial, anti-trypanosomal and anti-leishmanial drugs...
  4. doi request reprint Human African trypanosomiasis
    Reto Brun
    Department Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH 4002 Basel, Switzerland
    Infect Dis Clin North Am 26:261-73. 2012
    ..Elimination of the disease is considered feasible provided better tools for diagnosis and treatment can be made available...
  5. ncbi request reprint New developments in human African trypanosomiasis
    Reto Brun
    Swiss Tropical Institute, Parasite Chemotherapy, Basel, Switzerland
    Curr Opin Infect Dis 19:415-20. 2006
    ..To review recent literature on human African trypanosomiasis, focussing on genome sequencing, diagnosis and drug discovery, and typing of trypanosomes...
  6. doi request reprint 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...
  7. ncbi request reprint The story of CGP 40 215: studies on its efficacy and pharmacokinetics in African green monkey infected with Trypanosoma brucei rhodesiense
    R Brun
    Swiss Tropical Institute, Basel, Switzerland
    Trop Med Int Health 6:362-8. 2001
    ..As the majority of sleeping sickness patients seeking treatment are in the 2nd stage of the disease, further development of the compound was stopped...
  8. ncbi request reprint 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...
  9. doi request reprint In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi
    Kirsten Gillingwater
    Parasite Chemotherapy, Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, 4002 Basel, Switzerland
    Vet Parasitol 169:264-72. 2010
    ..evansi in vitro. In addition, preliminary in vivo toxicity tests were performed on all 67 diamidines with 69% of the compounds showing no acute toxicity at an intra-peritoneal dose of 100mg/kg...
  10. pmc Pharmacokinetics, Trypanosoma brucei gambiense efficacy, and time of drug action of DB829, a preclinical candidate for treatment of second-stage human African trypanosomiasis
    Tanja Wenzler
    Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    Antimicrob Agents Chemother 57:5330-43. 2013
    ..In summary, DB829 is a promising preclinical candidate for the treatment of first- and second-stage HAT caused by both Trypanosoma brucei subspecies. ..
  11. doi request reprint Abietane diterpenoids from Salvia sahendica--antiprotozoal activity and determination of their absolute configurations
    Samad N Ebrahimi
    Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
    Planta Med 79:150-6. 2013
    ..falciparum, and from 1.8 µM to over 32.3 µM against T. brucei rhodesiense. The cytotoxic IC50 values ranged from 0.5-15.5 µM. Selectivity indices for P. falciparum were 0.1 to 18.2, and 0.1 to 1.2 for T. brucei rhodesiense...
  12. pmc Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol
    Fabrice E Graf
    Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland
    PLoS Negl Trop Dis 7:e2475. 2013
    ..b. gambiense carrying such mutations correlate with a significantly reduced susceptibility to pentamidine and melarsoprol. ..
  13. doi request reprint Cynaropicrin: the first plant natural product with in vivo activity against Trypanosoma brucei
    Stefanie Zimmermann
    Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, Basel, Switzerland
    Planta Med 78:553-6. 2012
    ..8, 62, and 9.5 were determined. This is the first report of a plant natural product with potent IN VIVO activity against TRYPANOSOMA BRUCEI...
  14. ncbi request reprint Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei
    Stefanie Zimmermann
    Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    Bioorg Med Chem 21:7202-9. 2013
    ..At the same time, the study provides a novel extraction and analysis protocol for components of the trypanosomal thiol metabolism. ..
  15. doi request reprint Antiparasitic agents: new drugs on the horizon
    Pascal Maser
    Swiss Tropical and Public Health Institute, 4003 Basel, Switzerland
    Curr Opin Pharmacol 12:562-6. 2012
    ..Thus, finally, new therapeutic agents against malaria and sleeping sickness are within reach...
  16. 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...
  17. doi request reprint In vitro assessment of the pharmacodynamic properties of DB75, piperaquine, OZ277 and OZ401 in cultures of Plasmodium falciparum
    Sandra Hofer
    Swiss Tropical Institute, Socinstrasse 57, CH 4002 Basel, Switzerland
    J Antimicrob Chemother 62:1061-4. 2008
    ....
  18. pmc In vivo investigations of selected diamidine compounds against Trypanosoma evansi using a mouse model
    Kirsten Gillingwater
    Parasite Chemotherapy, Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland
    Antimicrob Agents Chemother 53:5074-9. 2009
    ..After all selection criteria were applied, three diamidine compounds (DB 75, DB 867, and DB 1192) qualified as lead compounds and were considered to have the potential to act as preclinical candidates against T. evansi infection...
  19. doi request reprint Identification of a new chemical class of antimalarials
    Ralf Brunner
    Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel CH 4002, Switzerland
    J Infect Dis 206:735-43. 2012
    ..falciparum SCID mouse model. ACT-213615 represents a new class of potent antimalarials that merits further investigation for its clinical potential...
  20. pmc Isothermal microcalorimetry, a new tool to monitor drug action against Trypanosoma brucei and Plasmodium falciparum
    Tanja Wenzler
    Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    PLoS Negl Trop Dis 6:e1668. 2012
    ..The method could probably be adapted to other protozoan parasites, especially those growing extracellularly...
  21. pmc In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models
    Sarah Schleiferböck
    Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland
    Drug Des Devel Ther 7:1377-84. 2013
    ..SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile. ..
  22. pmc Novel diamidines with activity against Babesia divergens in vitro and Babesia microti in vivo
    Angela Nehrbass-Stuedli
    Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    Antimicrob Agents Chemother 55:3439-45. 2011
    ..5 and/or 25 mg/kg of body weight given by the subcutaneous route for 4 days. The best antibabesial properties were exhibited by terphenyls, benzimidazoles, diphenyl furans, pentamidine, and pentamidine analogues...
  23. pmc UV-triggered affinity capture identifies interactions between the Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) and antimalarial agents in live parasitized cells
    Ralf Brunner
    Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH 4002 Basel, Switzerland
    J Biol Chem 288:22576-83. 2013
    ..We surmise that PfMDR1 may play a role in the antimalarial activity of the piperazine-containing compound ACT-213615. ..
  24. pmc Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness
    Marcel Kaiser
    Swiss Tropical and Public Health Institute, Parasite Chemotherapy, Socinstrasse 57, CH 4002 Basel, Switzerland
    Antimicrob Agents Chemother 55:5602-8. 2011
    ..b. gambiense and T. b. rhodesiense forms of human sleeping sickness and both stages of the disease...
  25. pmc A new double-antibody sandwich ELISA targeting Plasmodium falciparum aldolase to evaluate anti-malarial drug sensitivity
    Lucienne Tritten
    Swiss Tropical Institute, Socinstrasse 57, CH 4002 Basel, Switzerland
    Malar J 8:226. 2009
    ..Several other ways to evaluate in vitro anti-malarial activity do exist, all with their own assets and limitations...
  26. ncbi request reprint Melarsoprol- and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance
    Sonja C Bernhard
    Swiss Tropical Institute, Socinstr 57, Basel, Switzerland
    Int J Parasitol 37:1443-8. 2007
    ..The melarsoprol-selected population apparently had lost TbAT1, whereas in the pentamidine-selected trypanosome population it was still present...
  27. ncbi request reprint Eflornithine for the treatment of human African trypanosomiasis
    Christian Burri
    Swiss Tropical Institute, Swiss Center for International Health, Socinstrasse 57, P O Box, 4002 Basel, Switzerland
    Parasitol Res 90:S49-52. 2003
    ..Based on its trypanostatic rather than trypanocidal mode of action, it is a rather slow-acting drug...
  28. doi request reprint Antiprotozoal isoflavan quinones from Abrus precatorius ssp. africanus
    Yoshie Hata
    Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
    Planta Med 79:492-8. 2013
    ..Compounds 3 and 4 showed strong activity against T. b. rhodesiense (IC50 values of 0.30 and 0.16 µM, respectively) and good selectivity (selectivity indices of 73.7 and 50.5, respectively)...
  29. pmc Spiroindolones, a potent compound class for the treatment of malaria
    Matthias Rottmann
    Swiss Tropical and Public Health Institute, Parasite Chemotherapy, CH 4002 Basel, Switzerland
    Science 329:1175-80. 2010
    ..The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model...
  30. pmc Trematocidal activity of praziquantel and artemisinin derivatives: in vitro and in vivo investigations with adult Echinostoma caproni
    Jennifer Keiser
    Swiss Tropical Institute, P O Box, CH 4002 Basel, Switzerland
    Antimicrob Agents Chemother 50:803-5. 2006
    ..In vivo, worm burden reductions of 100% were achieved with single oral doses of praziquantel, artesunate, and artemether at 50, 700, and 1,100 mg/kg of body weight, respectively...
  31. ncbi request reprint Trypanosoma evansi and T. equiperdum: distribution, biology, treatment and phylogenetic relationship (a review)
    R Brun
    Swiss Tropical Institute, Basel
    Vet Parasitol 79:95-107. 1998
    ..The phylogenetic relationship between the two species and T. b. brucei is being discussed, and the hypothesis is proposed that T. evansi arose from a clone of T. equiperdum which lost its maxicircles...
  32. ncbi request reprint Clinical and serologic responses to human 'apathogenic' trypanosomes
    J Blum
    Swiss Tropical Institute, Department of Medical and Diagnostic Services, Basel
    Trans R Soc Trop Med Hyg 99:795-7. 2005
    ..We performed serologic tests because the patient was worried about HAT after receiving tsetse bites. The possibilities of an infection with human 'apathogenic' trypanosomes such as T. b. brucei, T. congolense or T. vivax are discussed...
  33. ncbi request reprint Establishment of a panel of reference Trypanosoma evansi and Trypanosoma equiperdum strains for drug screening
    K Gillingwater
    Parasite Chemotherapy, Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, 4002 Basel, Switzerland
    Vet Parasitol 148:114-21. 2007
    ..This panel of characterised strains with known drug sensitivities and resistances will be of great value for the screening of new active compounds, in comparison with the four standard drugs currently available...
  34. ncbi request reprint Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense: a randomised trial
    C Burri
    Swiss Tropical Institute, Basel
    Lancet 355:1419-25. 2000
    ..Despite these problems, melarsoprol is likely to remain the drug of choice for the next decade. We therefore did a randomised trial comparing the standard treatment schedule with a new, concise regimen...
  35. pmc Bottlenecks and the maintenance of minor genotypes during the life cycle of Trypanosoma brucei
    Michael Oberle
    Swiss Tropical and Public Health Institute, Basel, Switzerland
    PLoS Pathog 6:e1001023. 2010
    ..This is compatible with the epidemic population structure of T. brucei, in which clonal expansion of a few genotypes in a region occurs against a background of frequent recombination between strains...
  36. doi request reprint Development of novel drugs for human African trypanosomiasis
    Reto Brun
    Department Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and, University of Basel, CH 4002 Basel, Switzerland
    Future Microbiol 6:677-91. 2011
    ..With other screening programs yielding hits, the pipeline for new HAT drugs might finally begin to fill...
  37. ncbi request reprint Production of metacyclic forms by cyclical transmission of west African Trypanosoma (T.) brucei isolates from man and animals
    D Richner
    Swiss Tropical Institute, Basel
    Acta Trop 45:309-19. 1988
    ....
  38. pmc Peroxide bond-dependent antiplasmodial specificity of artemisinin and OZ277 (RBx11160)
    Marcel Kaiser
    Swiss Tropical Institute, Basel, Switzerland
    Antimicrob Agents Chemother 51:2991-3. 2007
    ..In contrast, the weak activities of artemisinin and OZ277 against six other protozoan parasites were peroxide bond independent. These data support the iron-dependent artemisinin alkylation hypothesis...
  39. ncbi request reprint The isoenzyme characteristics of Trypanosoma evansi and Trypanosoma equiperdum isolated from domestic stocks in China
    Z R Lun
    Swiss Tropical Institute, Basel
    Ann Trop Med Parasitol 86:333-40. 1992
    ..Two other stocks of T. evansi and again the T. equiperdum, all from equines, showed a new pattern ALAT-14. Otherwise the Chinese stocks had the same enzyme profile as T. evansi from elsewhere...
  40. ncbi request reprint Isolation and propagation of Trypanosoma brucei gambiense from sleeping sickness patients in south Sudan
    Naomi W N Maina
    Trypanosomiasis Research Centre TRC of KARI, PO Box 362, Kikuyu, Kenya
    Trans R Soc Trop Med Hyg 101:540-6. 2007
    ..These results indicate that propagation of T. b. gambiense isolates after initial isolation in immunosuppressed M. natalensis or SCID mice can be done in a range of immunosuppressed rodents...
  41. pmc Diphenyl furans and aza analogs: effects of structural modification on in vitro activity, DNA binding, and accumulation and distribution in trypanosomes
    Amanda M Mathis
    Molecular Pharmaceutics, UNC School of Pharmacy, 3312 Kerr Hall, CB 7360, Chapel Hill, NC 27599, USA
    Antimicrob Agents Chemother 51:2801-10. 2007
    ..This investigation suggests that the extent of accumulation alone is not responsible for killing trypanosomes and that organelle-specific accumulation may not predict in vitro activity...
  42. ncbi request reprint Synthesis and antiprotozoal activity of aza-analogues of furamidine
    Mohamed A Ismail
    Department of Chemistry, Georgia State University, Atlanta, Georgia 30303 3083, USA
    J Med Chem 46:4761-9. 2003
    ..of less than 10 nM. Against P. f. 8a, 8b, and 14b exhibited IC(50) values less than 10 nM. In an in vivo mouse model for T. b. r. four compounds 6a, 6c, 6d, and 8a were curative. Compound 6a produced cures at an oral dosage of 5 mg/kg...
  43. ncbi request reprint Detection of arsenical drug resistance in Trypanosoma brucei with a simple fluorescence test
    Mhairi L Stewart
    University of Glasgow, Division of Infection and Immunity, Institute of Biomedical and Life Sciences, The Joseph Black Building, Glasgow G12 8QQ, UK
    Lancet 366:486-7. 2005
    ..The two DNA-containing structures in the trypanosome--the nucleus and the kinetoplast--begin to fluoresce within 1 min of introduction of DB99, unless drug resistant...
  44. ncbi request reprint 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...
  45. ncbi request reprint In vitro antitrypanosomal activity of ethnopharmacologically selected Beninese plants
    Sara Hoet
    Laboratoire de Pharmacognosie, Universite Catholique de Louvain, Av E Mounier 72, UCL 72 30 CHAM, B 1200 Brussels, Belgium
    J Ethnopharmacol 91:37-42. 2004
    ..The presence of flavonoids and quinones may at least in part explain the observed activities of some of the active extracts...
  46. pmc Mechanisms of arsenical and diamidine uptake and resistance in Trypanosoma brucei
    Enock Matovu
    Institute of Cell Biology, CH 3012 Bern, Switzerland
    Eukaryot Cell 2:1003-8. 2003
    ..High-level arsenical resistance therefore appears to involve the loss of more than one transporter...
  47. doi request reprint New bis(2-aminoimidazoline) and bisguanidine DNA minor groove binders with potent in vivo antitrypanosomal and antiplasmodial activity
    Fernando Rodriguez
    Centre for Synthesis and Chemical Biology, School of Chemistry, Trinity College Dublin, Dublin 2, Ireland
    J Med Chem 51:909-23. 2008
    ..No correlation between antiplasmodial activity and in vitro inhibition of ferriprotoporphyrin IX biomineralisation was observed, suggesting that additional mechanism of action is likely to be involved...
  48. ncbi request reprint Synthesis and in vitro antiprotozoal activities of water-soluble, inexpensive 3,7-bis(dialkylamino)phenoxazin-5-ium derivatives
    Jian Feng Ge
    Institute of Medicinal Chemistry, Hoshi University, 2 4 41 Ebara, Shinagawa ku, Tokyo 142 8501, Japan
    J Med Chem 51:3654-8. 2008
    ..Notably, the compounds showed potent antiprotozoal activities, especially against P. falciparum and T. cruzi. The compounds with alkyl side chains less than three carbons in length possessed good activities with high selective indices...
  49. ncbi request reprint Synthesis of bicyclic amines and their activities against Trypanosoma brucei rhodesiense and Plasmodium falciparum K1
    Robert Weis
    Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl Franzens University, Universitatsplatz 1, A 8010, Graz, Austria
    Arch Pharm Res 31:688-97. 2008
    ..2.2]nonanes. Some of the 4-aminobicyclo[2.2.2]oct-2-ylamines exhibit moderate in vivo activity in mice against Trypanosoma brucei brucei...
  50. ncbi request reprint Synthesis and evaluation of the antitrypanosomal and antiplasmodial activities of new 4-aminobicyclo[2.2.2]octane derivatives
    Werner Seebacher
    Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl Franzens University, Universitatsplatz 1, A 8010 Graz, Austria
    Eur J Med Chem 40:888-96. 2005
    ..The methylthiosemicarbazones show moderate antiprotozoal activities whereas some of the esters of piperonylic acid, homopiperonylic acid and 2-naphtoic acid exhibit remarkable antitrypanosomal and antiplasmodial activity...
  51. ncbi request reprint O-alkoxyamidine prodrugs of furamidine: in vitro transport and microsomal metabolism as indicators of in vivo efficacy in a mouse model of Trypanosoma brucei rhodesiense infection
    John H Ansede
    Division of Drug Delivery and Disposition, School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7360, USA
    J Med Chem 47:4335-8. 2004
    ..Permeability across Caco-2 cell monolayers and microsomal metabolism were used to identify the underlying mechanisms of prodrug efficacy...
  52. ncbi request reprint Synthesis and in vitro antiprotozoal activities of dicationic 3,5-diphenylisoxazoles
    Donald A Patrick
    Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7525, USA
    J Med Chem 50:2468-85. 2007
    ..Fourteen of these compounds had cytotoxic indices ranging between 10 and 120 times higher than that of furamidine, and five analogues exhibited high selectivity for P. falciparum over T. brucei rhodesiense...
  53. ncbi request reprint Design and synthesis of a series of melamine-based nitroheterocycles with activity against Trypanosomatid parasites
    Alessandro Baliani
    Welsh School of Pharmacy, Redwood Building, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, United Kingdom
    J Med Chem 48:5570-9. 2005
    ..cruzi against which various nitro heterocycles are already registered for use...
  54. ncbi request reprint Plasmodium vivax: in vitro susceptibility of blood stages to synthetic trioxolane compounds and the diamidine DB75
    Clemens H M Kocken
    Biomedical Primate Research Centre, Department of Parasitology, P O Box 3306, 2280 GH Rijswijk, The Netherlands
    Exp Parasitol 113:197-200. 2006
    ..These data warrant clinical testing of OZ277 against P. vivax malaria and support recent data on clinical activity against P. vivax for DB75...
  55. ncbi request reprint Synthesis, DNA affinity, and antiprotozoal activity of linear dications: Terphenyl diamidines and analogues
    Mohamed A Ismail
    Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, Georgia 30303 3083, USA
    J Med Chem 49:5324-32. 2006
    ..Mouse liver microsome bioconversion of the methamidoxime prodrugs is significantly reduced from that of pafuramidine and suggests that the in vivo efficacy of these prodrugs is, in part, due to poor bioconversion...
  56. ncbi request reprint The role of Trypanosoma brucei MRPA in melarsoprol susceptibility
    Vincent P Alibu
    Universitat Heidelberg, Zentrum für Molekulare Biologie ZMBH, Im Neuenheimer Feld 282, D69120 Heidelberg, Germany
    Mol Biochem Parasitol 146:38-44. 2006
    ..Over-expression of MRPA was not detected in four melarsoprol-resistant trypanosome isolates from sleeping sickness patients...
  57. ncbi request reprint DNA binding affinity of bisguanidine and bis(2-aminoimidazoline) derivatives with in vivo antitrypanosomal activity
    Christophe Dardonville
    Instituto de Química Médica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain
    J Med Chem 49:3748-52. 2006
    ..From these studies, the 4,4'-diaminodiphenylamine skeleton emerged as a good scaffold for antitrypanosomal drugs...
  58. ncbi request reprint Ancistrotanzanine C and related 5,1'- and 7,3'-coupled naphthylisoquinoline alkaloids from Ancistrocladus tanzaniensis
    Gerhard Bringmann
    Institut für Organische Chemie der Universität Würzburg, Am Hubland, D 97074 Wurzburg, Germany
    J Nat Prod 67:743-8. 2004
    ..The biological activities of the alkaloids against the pathogens causing malaria tropica, leishmaniasis, Chagas' disease, and African sleeping sickness were evaluated...
  59. ncbi request reprint Gaboroquinones A and B and 4'-O-demethylknipholone-4'-O-beta-D-glucopyranoside, phenylanthraquinones from the roots of Bulbine frutescens
    Berhanu M Abegaz
    Department of Chemistry, University of Botswana, Private Bag 0022, Gaborone, Botswana
    J Nat Prod 65:1117-21. 2002
    ..Compounds 2, 3, and 4 showed moderate to good antiplasmodial and antitrypanosomal activities in vitro...
  60. ncbi request reprint Antimalarial drug discovery: efficacy models for compound screening
    David A Fidock
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Nat Rev Drug Discov 3:509-20. 2004
  61. ncbi request reprint Ancistrocongolines A-D, new naphthylisoquinoline alkaloids from ancistrocladus congolensis
    Gerhard Bringmann
    Institut für Organische Chemie der Universität, Am Hubland, D 97074 Wurzburg, Germany
    J Nat Prod 65:1096-101. 2002
    ..Structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. Their biological activities against the pathogens of malaria, Leishmaniasis, Chagas disease, and African sleeping sickness were evaluated...
  62. ncbi request reprint Novel dicationic imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridines as antiprotozoal agents
    Mohamed A Ismail
    Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303 3083, USA
    J Med Chem 47:3658-64. 2004
    ..The oral activity of the prodrugs was modest with only one showing 2/4 cures in the same mouse model...
  63. ncbi request reprint Alkaloids from Narcissus angustifolius subsp. transcarpathicus (Amaryllidaceae)
    Josep Labraña
    Departament de Productes Naturals, Facultat de Farmacia, Universitat de Barcelona, Avda Diagonal 643, E 08028 Barcelona, Spain
    Phytochemistry 60:847-52. 2002
    ..The in vitro assay activity against the parasitic protozoa Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum was carried out with the compounds nangustine and pancracine...
  64. ncbi request reprint Identification of an antimalarial synthetic trioxolane drug development candidate
    Jonathan L Vennerstrom
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    Nature 430:900-4. 2004
    ..Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project...
  65. ncbi request reprint 2,4-Diaminopyrimidines as inhibitors of Leishmanial and Trypanosomal dihydrofolate reductase
    Didier Pez
    Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF Cardiff, UK
    Bioorg Med Chem 11:4693-711. 2003
    ..The leishmanial enzyme was found to have a more extensive lipophilic binding region in the active site than the human enzyme. Compounds which bound within the pocket showed the highest selectivity...
  66. pmc Trypanocidal activity of melamine-based nitroheterocycles
    Mhairi L Stewart
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
    Antimicrob Agents Chemother 48:1733-8. 2004
    ..brucei, distinguishing it from some other, mammalian cell toxic, trypanocidal nitroheterocycles...
  67. ncbi request reprint Anti-trypanosomal activity of helenalin and some structurally related sesquiterpene lactones
    Thomas J Schmidt
    Institut für Pharmazeutische Biologie der Heinrich Heine Universität, Dusseldorf, Germany
    Planta Med 68:750-1. 2002
    ..051 and 0.695 microM against T. brucei rhodesiense and T. cruzi, respectively. The low IC50 value for T. b. rhodesiense indicates that helenalin type compounds may be interesting candidates for further evaluation...
  68. ncbi request reprint Synthesis and biological evaluation of pyrazolylnaphthoquinones as new potential antiprotozoal and cytotoxic agents
    Norma R Sperandeo
    Departamento de Farmacia, Facultad de Ciencias Quimicas, Universidad Nacional de Córdoba 5000 Córdoba, Argentina
    Chembiochem 4:69-72. 2003
    ..21-0.50 microg mL(-1)). The results suggested that the three pyrazolylnaphthoquinones and one of the 5-aminoisoxazole analogues could be starting points for lead optimization programs against T. cruzi and P. falciparum, respectively...
  69. ncbi request reprint New 4-aminobicyclo[2.2.2]octane derivatives and their activities against Plasmodium falciparum and Trypanosoma b. rhodesiense
    Werner Seebacher
    Institute of Pharmaceutical Chemistry and Pharmaceutical Technology, Karl Franzens University, Universitatsplatz 1, A 8010, Graz, Austria
    Eur J Pharm Sci 21:225-33. 2004
    ..68microM) of the so far prepared 4-amino-6,7-diarylbicyclo[2.2.2]octane derivatives, but is distinctly less active than suramin (IC(50)=0.0075microM)...
  70. ncbi request reprint Antifungal, antiprotozoal, cytotoxic and piscicidal properties of Justicidin B and a new arylnaphthalide lignan from Phyllanthus piscatorum
    Jürg Gertsch
    Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology ETH Zurich, Zurich, Switzerland
    Planta Med 69:420-4. 2003
    ..Both compounds were piscicidal against zebra fish and it is shown for the first time that piscatorin (2) and justicidin B (1) are the piscicidal principles of P. piscatorum, exhibiting a potency that is comparable to rotenone...
  71. ncbi request reprint Synthesis and biological evaluation of substrate-based inhibitors of 6-phosphogluconate dehydrogenase as potential drugs against African trypanosomiasis
    Christophe Dardonville
    Welsh School of Pharmacy, Redwood Building, Cardiff University, King Edward VII Avenue, CF10 3XF, Cardiff, UK
    Bioorg Med Chem 11:3205-14. 2003
    ..The trypanocidal effect of the compounds was also evaluated in vitro against T. brucei rhodesiense as well as other related trypanosomatid parasites (i.e., Trypanosoma cruzi and Leishmania donovani)...
  72. ncbi request reprint Bisguanidine, bis(2-aminoimidazoline), and polyamine derivatives as potent and selective chemotherapeutic agents against Trypanosoma brucei rhodesiense. Synthesis and in vitro evaluation
    Christophe Dardonville
    Instituto de Química Médica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain
    J Med Chem 47:2296-307. 2004
    ..g. 1c (IC(50) = 49 nM; SI > 5294), 28b (IC(50) = 69 nM; SI = 3072), 32b (IC(50) = 22 nM; SI = 29.5), 41b (IC(50) = 118 nM; SI = 881)] represent new antitrypanosomal lead compounds...
  73. ncbi request reprint Synthesis and evaluation of novel 7-trifluoromethyl-4-(4-substituted anilino)quinolines as antiparasitic and antineoplastic agents
    Ashraf H Abadi
    Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
    Arzneimittelforschung 53:655-63. 2003
    ..However, the pattern for the antitumor activity did not parallel any of the antiparasitic ones, indicating that non-common mechanisms of action may exist among these activities...
  74. ncbi request reprint Inhibiting activities of the secondary metabolites of Phlomis brunneogaleata against parasitic protozoa and plasmodial enoyl-ACP Reductase, a crucial enzyme in fatty acid biosynthesis
    Hasan Kirmizibekmez
    Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
    Planta Med 70:711-7. 2004
    ..falciparum, was also assessed. Compound 10 showed promising FabI inhibiting effect (IC (50) = 10 micrograms/mL) and appears to be the first anti-malarial natural product targeting FabI of P. falciparum...
  75. ncbi request reprint Anthranoid compounds with antiprotozoal activity from Vismia orientalis
    Zakaria H Mbwambo
    Institute of Traditional Medicine, Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania
    Planta Med 70:706-10. 2004
    ..b. rhodesiense, L. donovani and P. falciparum were in the range of 10 to 50 micrograms/mL. None of the compounds showed antibacterial or antiviral (including also HIV) activity...
  76. ncbi request reprint Synthesis and antimalarial property of orally active phenoxazinium salts
    Kiyosei Takasu
    J Med Chem 50:2281-4. 2007
    ..They also showed excellent potency by oral administration. A preliminary pharmacokinetic study revealed that the oral availability of 1a was excellent...
  77. pmc Interaction of monobenzamidine-linked trypanocides with the Trypanosoma brucei P2 aminopurine transporter
    Mhairi L Stewart
    University of Glasgow, Institute of Biomedical and Life Sciences, Division of Infection and Immunity, Glasgow G12 8QQ, United Kingdom
    Antimicrob Agents Chemother 49:5169-71. 2005
    ..Trypanocidal activity was evident, but compounds were equally toxic against trypanosomes lacking the P2 transporter, which indicates additional uptake routes for monobenzamidine-derived compounds...
  78. ncbi request reprint Dicationic DNA-targeted antiprotozoal agents: naphthalene replacement of benzimidazole
    Sarah Chackal-Catoen
    Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303 3083, USA
    Bioorg Med Chem 14:7434-45. 2006
    ..The amidoxime prodrugs of the naphthalene analogues were essentially ineffective...
  79. ncbi request reprint Antiprotozoal activities of new bis-chlorophenyl derivatives of bicyclic octanes and aza-nonanes
    Heinrich Berger
    Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl Franzens University, Universitatsplatz 1, A 8010 Graz, Austria
    Bioorg Med Chem Lett 16:5457-61. 2006
    ..Especially the bis-(chlorophenyl)-azabicyclo[3.2.2]nonanes exhibit promising antitrypanosomal activity and were tested in vivo against Trypanosoma brucei brucei featuring moderate activities...
  80. ncbi request reprint Deoxyuridine triphosphate nucleotidohydrolase as a potential antiparasitic drug target
    Corinne Nguyen
    Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3XF, UK
    J Med Chem 48:5942-54. 2005
    ..falciparum dUTPase constitutes a valid and attractive novel target for the development of much-needed new antimalarial drugs...
  81. ncbi request reprint Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids
    Deniz Tasdemir
    University of Zurich, Institute of Organic Chemistry, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    J Med Chem 49:3345-53. 2006
    ..In addition, these polyphenols showed in vitro activity against chloroquine-sensitive (NF54) and -resistant (K1) P. falciparum strains in the low to submicromolar range...
  82. ncbi request reprint Design, synthesis and evaluation of novel uracil amino acid conjugates for the inhibition of Trypanosoma cruzi dUTPase
    Orla K Mc Carthy
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    Bioorg Med Chem Lett 16:3809-12. 2006
    ....
  83. ncbi request reprint 3D QSAR on a library of heterocyclic diamidine derivatives with antiparasitic activity
    Prashanth Athri
    Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
    Bioorg Med Chem 14:3144-52. 2006
    ..699, r2=0.974, SEE, standard error of estimate=0.1, and F=120.04. The results have been used as a guide to design compounds that, potentially, have better activity against African trypanosomes...
  84. ncbi request reprint Solid phase synthesis and antiprotozoal evaluation of di- and trisubstituted 5'-carboxamidoadenosine analogues
    Boris Rodenko
    van t Hoff Institute for Molecular Sciences, Universiteit van Amsterdam, The Netherlands
    Bioorg Med Chem 14:1618-29. 2006
    ..91 microM against Trypanosoma brucei rhodesiense and N(6)-diphenylethyl-5'-phenylcarboxamidoadenosine with an IC(50) value of 1.8 microM against chloroquine resistant Plasmodium falciparum...
  85. ncbi request reprint Synthesis, DNA affinity, and antiprotozoal activity of fused ring dicationic compounds and their prodrugs
    Reem K Arafa
    Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, Georgia 30303 3083, USA
    J Med Chem 48:5480-8. 2005
    ..In contrast, a number of the carbamates showed promising activity. The value of the carbamate prodrugs was clearly demonstrated by the results, which gave 4/4 cures on oral administration in the STIB900 mouse model...
  86. ncbi request reprint ent-Dioncophylleine A and related dehydrogenated naphthylisoquinoline alkaloids, the first Asian dioncophyllaceae-type alkaloids, from the "new"plant species Ancistrocladus benomensis
    Gerhard Bringmann
    Institut für Organische Chemie der Universität Würzburg, Am Hubland, D 97074 Wurzburg, Germany
    J Nat Prod 68:686-90. 2005
    ..The structural elucidation was achieved by spectroscopic and chiroptical methods. Biological activities of these alkaloids against different protozoan parasites are described...
  87. ncbi request reprint Antiprotozoal activities of new bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols
    Werner Seebacher
    Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl Franzens University, Universitatsplatz 1, A 8010 Graz, Austria
    Eur J Pharm Sci 24:281-9. 2005
    ..2.2]octan-2-yl benzoate exhibit attractive antimalarial activity (IC(50)=0.23-0.72 microM). Two bicyclooctanone oximes are even as active as chloroquine (IC(50)=0.08-0.15 microM, chloroquine: IC(50)=0.12 microM against sensitive strains)...
  88. ncbi request reprint Design, synthesis and evaluation of 2,4-diaminoquinazolines as inhibitors of trypanosomal and leishmanial dihydrofolate reductase
    Soghra Khabnadideh
    Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3XF, UK
    Bioorg Med Chem 13:2637-49. 2005
    ..There was significantly lower activity against Leishmania donovani, one of the causative organisms of leishmaniasis...
  89. doi request reprint Potent and selective antiplasmodial activity of the cyanobacterial alkaloid nostocarboline and its dimers
    Damien Barbaras
    Laboratorium fur Organische Chemie, Swiss Federal Institute of Technology ETH, 8093 Zurich, Switzerland
    Bioorg Med Chem Lett 18:4413-5. 2008
    ..Selectivity against rat myoblasts (L6 cells) was found to be up to >2500-fold...
  90. ncbi request reprint Novel azabicyclo[3.2.2]nonane derivatives and their activities against Plasmodium falciparum K1 and Trypanosoma brucei rhodesiense
    Heinrich Berger
    Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl Franzens University, Universitatsplatz 1, A 8010 Graz, Austria
    Bioorg Med Chem 16:6371-8. 2008
    ..Some of the new compounds are amongst the most active antitrypanosomal agents in this series, and the selectivity index of a single derivative is superior in the 2-azabicyclo-nonane series...
  91. pmc Host cells participate in the in vitro effects of novel diamidine analogues against tachyzoites of the intracellular apicomplexan parasites Neospora caninum and Toxoplasma gondii
    Angela Leepin
    Institute of Parasitology, University of Bern, Langgass strasse 122, CH 3012 Bern, Switzerland
    Antimicrob Agents Chemother 52:1999-2008. 2008
    ....
  92. doi request reprint Malaria-infected mice are cured by oral administration of new artemisinin derivatives
    Gary H Posner
    Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218 2685, USA
    J Med Chem 51:1035-42. 2008
    ..7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase II clinical trials...
  93. ncbi request reprint Joziknipholones A and B: the first dimeric phenylanthraquinones, from the roots of Bulbine frutescens
    Gerhard Bringmann
    Institut fur Organische Chemie, Universitat Wurzburg, Am Hubland, Wurzburg, Germany
    Chemistry 14:1420-9. 2008
    ..Joziknipholones A and B are active against the chloroquine resistant strain K1 of the malaria pathogen, Plasmodium falciparum, and show moderate activity against murine leukemic lymphoma L5178y cells...
  94. ncbi request reprint Synthesis and in vitro antiprotozoal activity of bisbenzofuran cations
    Svetlana M Bakunova
    Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina, Chapel Hill, NC 27599 7525, USA
    J Med Chem 50:5807-23. 2007
    ..Eight bisbenzofurans displayed activity against L. donovani superior to that of pentamidine. Overall, bisamidines connected by two-carbon linkers exhibited the highest efficacies against T. b. rhodesiense, P. falciparum, and L. donovani...
  95. ncbi request reprint Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes
    Yuxiang Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
    Bioorg Med Chem 14:6368-82. 2006
    ..More lipophilic trioxolanes tended to have better oral activities than their more polar counterparts. Trioxolanes with a wide range of neutral and basic, but not acidic, functional groups had good antimalarial profiles...
  96. ncbi request reprint Synthesis of 2-azabicyclo[3.2.2]nonanes from bicyclo[2.2.2]octan-2-ones and their activities against Trypanosoma brucei rhodesiense and Plasmodium falciparum K1
    Werner Seebacher
    Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl Franzens University, A 8010 Graz, Austria
    J Pharm Pharm Sci 8:578-85. 2005
    ..2.2]octan-2-ones to investigate the influence of the replacement of the rigid bicyclo-octane structure by the more flexible bicyclo-nonane system on the antiplasmodial and antitrypanosomal activity...