In vitro antifungal activity of DNA topoisomerase inhibitorsDietmar Steverding
Norwich Medical School, University of East Anglia, Norwich, UK
Med Mycol 50:333-6. 2012
..glabrata and C. neoformans with MIC(50) values in the mid micromolar range. The data of this study indicate that selected DNA topoisomerase inhibitors are a promising class of compounds for the development of new antifungal agents...
- Trypanocidal activity of ?-lactone-?-lactam proteasome inhibitors
Dietmar Steverding
Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, UK
Planta Med 78:131-4. 2012
..In general, trypanosomes were more susceptible to the compounds than were human HL-60 cells. The data support the potential of ?-lactone- ?-lactam proteasome inhibitors for rational anti-trypanosomal drug development...
- Ochronosis as an unusual cause of valvular defect: a case report
Andreas Wilke
Kardiologische Praxis Papenburg, Papenburg, Germany
J Med Case Reports 3:9302. 2009
..Alkaptonuria (also known as ochronosis) is a genetic disorder characterised by the accumulation of homogentisic acid deposits in connective tissue. In rare cases, ochronosis can cause valvular heart disease...
- Cysteine proteinase inhibitors as therapy for parasitic diseases: advances in inhibitor design
Dietmar Steverding
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK
Mini Rev Med Chem 6:1025-32. 2006
..This article reviews the biology and physicochemistry of parasite proteinases and the ongoing design of peptidyl and non-peptidyl inhibitors to generate anti-parasitic compounds of greater efficacy with decreased toxicity to the host...
- Evaluation of the anti-trypanosomal activity of tyropeptin A
Dietmar Steverding
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK
Planta Med 72:761-3. 2006
..The results suggest that natural compounds targeting the trypsin-like activity of the proteasome may serve as leads for rational drug development of novel anti-trypanosomal agents...
- On the role of blue shadows in the visual behaviour of tsetse flies
Dietmar Steverding
School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, UK
Proc Biol Sci 271:S16-7. 2004
..In contrast to people's experience that daytime shadows are colourless, actually on a sunny day all shadows are tinted bluish by the scattered blue skylight...
- Ubiquitination of plasma membrane ectophosphatase in bloodstream forms of Trypanosoma brucei
D Steverding
Abteilung Parasitologie, Hygiene Institut der Ruprecht Karls Universtät, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
Parasitol Res 98:157-61. 2006
..As ubiquitin modification of plasma membrane proteins serves as an internalization signal, it is suggested that ubiquitinated ectophosphatase is labelled for endocytosis...
- Trypanosoma brucei: unexpected azide sensitivity of bloodstream forms
Dietmar Steverding
School of Biological Sciences, University of Bristol, Bristol BS8 1UG, UK
J Parasitol 90:1188-90. 2004
..5 mM azide (a concentration at which no cell proliferates), the toxic action of azide cannot be due to inhibition of this enzyme. These results indicate that the general toxicity of azide is different from that of cyanide...
- Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors
Dietmar Steverding
School of Biological Sciences, University of Bristol, Woodland Road, Bristol, BS8 1UG, UK
Parasitol Res 95:73-6. 2005
..These data suggest that inhibitors with strong activity against the trypsin-like activity of the proteasome are the rational choice for future anti-sleeping sickness drug development...
- Effect of Australian tea tree oil on Gyrodactylus spp. infection of the three-spined stickleback Gasterosteus aculeatus
Dietmar Steverding
School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, UK
Dis Aquat Organ 66:29-32. 2005
..In addition, Tween 80 alone exhibited parasiticidal activity against Gyrodactylus spp. These findings show the potential of TTO in combination with Tween 80 as an effective treatment of Gyrodactylus spp. infection of fishes...
- The significance of transferrin receptor variation in Trypanosoma brucei
Dietmar Steverding
School of Biological Sciences, University of Bristol, Woodland Road, Bristol, UK BS8 1UG
Trends Parasitol 19:125-7. 2003
..This article shows that calculations based on K(d) values argue against the first part of the hypothesis, but might support the second part...
- On the significance of host antibody response to the Trypanosoma brucei transferrin receptor during chronic infection
Dietmar Steverding
School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK
Microbes Infect 8:2777-82. 2006
..Altogether, the results suggest that the host antibody response to the TbTfR during chronic infection with T. brucei is too low, if present at all, to prevent sufficient iron uptake by bloodstream forms to promote their growth...
- Trypanocidal activity of peptidyl vinyl ester derivatives selective for inhibition of mammalian proteasome trypsin-like activity
Dietmar Steverding
Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom
Exp Parasitol 128:444-7. 2011
..This finding shows that the inhibitor sensitivities between mammalian and trypanosome proteasome are distinct. This difference may be exploited for rational anti-trypanosomal drug development...
- The development of drugs for treatment of sleeping sickness: a historical review
Dietmar Steverding
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK
Parasit Vectors 3:15. 2010
..This review summarises the developmental processes which led to these chemotherapies from the discovery of the first bioactive lead compounds to the identification of the final drugs...
- The trypanocidal effect of NO-releasing agents is not due to inhibition of the major cysteine proteinase in Trypanosoma brucei
Dietmar Steverding
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK
Parasitol Res 105:1333-8. 2009
..The results show that the trypanocidal activity of NO donors cannot be attributed to the inhibition of the major lysosomal cysteine proteinase in bloodstream forms of T. brucei...
- Trypanocidal activity of the proteasome inhibitor and anti-cancer drug bortezomib
Dietmar Steverding
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, NR4 7TJ, UK
Parasit Vectors 2:29. 2009
..The results suggest that bortezomib may be useful as drug for the treatment of human African trypanosomiasis...
- Efficacy of common laboratory disinfectants and heat on killing trypanosomatid parasites
Xia Wang
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, NR4 7TJ, UK
Parasit Vectors 1:35. 2008
..The results indicate that the disinfectants, water and temperature treatment (i.e. autoclaving) are suitable laboratory hygiene measures against trypanosomatid parasites...
- The history of African trypanosomiasis
Dietmar Steverding
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK
Parasit Vectors 1:3. 2008
..Current history of human African trypanosomiasis has shown that the production of anti-sleeping sickness drugs is not always guaranteed, and therefore, new, better and cheaper drugs are urgently required...
- Novel antitrypanosomal agents
Dietmar Steverding
School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 TJ7, UK
Expert Opin Investig Drugs 14:939-55. 2005
..This article summarises the recent progress in identifying novel lead compounds for antitrypanosomal chemotherapy. Particular emphasis is placed on those agents showing promising, selective antitrypanosomal activity...
- Identification of a developmentally regulated iron superoxide dismutase of Trypanosoma brucei
M Kabiri
Abteilung Parasitologie, , Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany
Biochem J 360:173-7. 2001
....
- Trypanocidal effect of alpha',beta'-epoxyketones indicates that trypanosomes are particularly sensitive to inhibitors of proteasome trypsin-like activity
Robert J Glenn
School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, UK
Int J Antimicrob Agents 24:286-9. 2004
..In conclusion, the data suggests that proteasome inhibitors targeting the trypsin-like activity are the rational choice for future anti-trypanosomal drug development...
- Bloodstream forms of Trypanosoma brucei require only small amounts of iron for growth
D Steverding
Hygiene Institut der Ruprecht Karls Universität, Abteilung Parasitologie, Heidelberg, Germany
Parasitol Res 84:59-62. 1998
..Calculations revealed that accumulation of about 40,000 iron atoms during 1 generation-doubling time was sufficient for parasite multiplication...
- The transferrin receptor of Trypanosoma brucei
D Steverding
Abteilung Parasitologie, Hygiene Institut, Ruprecht Karls Universitat, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
Parasitol Int 48:191-8. 2000
..In this review, the structure, biochemical properties and function of the transferrin receptor of T. brucei are summarized and compared to the transferrin receptor of mammalian cells...
- Trypanosoma evansi: demonstration of a transferrin receptor derived from expression site-associated genes 6 and 7
M Kabiri
Abteilung Parasitologie, , Heidelberg, Germany
J Parasitol 87:1189-91. 2001
..evansi is completely inhibited with anti-T. brucei (ESAG6/7 heterodimer) antibodies. The demonstration of a functional ESAG6/7 transferrin receptor in T. evansi supports further its close relationship to T. brucei...
- Improved trypanocidal activities of cathepsin L inhibitors
Njinkeng Joseph Nkemgu
Abteilung Parasitologie, , Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
Int J Antimicrob Agents 22:155-9. 2003
..Also, all inhibitors blocked proteinolysis in the lysosome consistent with the inhibition of rhodesain/brucipain. In conclusion, the data support the potential of cathepsin L inhibitors for rational anti-trypanosomal drug development...
- In vitro trypanocidal activity of the anti-helminthic drug niclosamide
Karin Merschjohann
Department of Parasitology, Ruprecht Karls University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
Exp Parasitol 118:637-40. 2008
..b. brucei and T. congolense, respectively. The very low toxicity of niclosamide for mammals makes the compound interesting for drug development for African trypanosomiasis...
- Growth inhibition of bloodstream forms of Trypanosoma brucei by the iron chelator deferoxamine
Tanja Breidbach
Abteilung Parasitologie, , Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany
Int J Parasitol 32:473-9. 2002
..The results have implications for antitrypanosomal drug development based on specific intervention with the parasite's iron metabolism...
- Expression and purification of non-glycosylated Trypanosoma brucei transferrin receptor in insect cells
Alexander Maier
Department of Parasitology, Ruprecht Karls University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
Exp Parasitol 120:205-7. 2008
..The non-glycosylated ESAG6 and ESAG7 were capable of forming a heterodimer and of binding transferrin. This results shows that glycosylation is not necessary for synthesis of a functional T. brucei transferrin receptor...
- Antitrypanosomal activities of proteasome inhibitors
Njinkeng Joseph Nkemngu
Abteilung Parasitologie, , , Heidelberg, Germany
Antimicrob Agents Chemother 46:2038-40. 2002
..In general, trypanosomes were more susceptible to the compounds than were human HL-60 cells. The data support the potential of proteasome inhibitors for rational antitrypanosomal drug development...
- In vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T. congolense
K Merschjohann
Abteilung Parasitologie, Hygiene-Institut, , Heidelberg, Germany
Planta Med 67:623-7. 2001
..DNA intercalation in combination with protein biosynthesis inhibition, which is the major mode of action of the active alkaloids, could be responsible for the observed trypanocidal and cytotoxic effects...
- Increased trypanolytic activity in sera of sleeping sickness patients after chemotherapy
A Fischer
Abteilung Parasitologie, , Heidelberg, Germany
Trop Med Int Health 6:1070-4. 2001
..These results suggest that trypanolytic activity of sera increases after African sleeping sickness and is directed against trypanosomes expressing metacyclic VSG...
- Identification and functional characterization of thioredoxin from Trypanosoma brucei brucei
N Reckenfelderbäumer
Biochemie Zentrum Heidelberg, Universitat Heidelberg, 69120 Heidelberg, Germany
J Biol Chem 275:7547-52. 2000
..brucei ribonucleotide reductase. The parasite protein is the first classical thioredoxin of the order Kinetoplastida characterized so far...
- Anti-trypanosomal activities of DNA topoisomerase inhibitors
Alexander Deterding
School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, United Kingdom
Acta Trop 93:311-6. 2005
..These data support the use of DNA topoisomerase inhibitors as lead compounds for anti-trypanosomal drug development...
- Trypanosoma brucei: in vitro slender-to-stumpy differentiation of culture-adapted, monomorphic bloodstream forms
Tanja Breidbach
Abteilung Parasitologie, , Im Neuenheimer Feld, Heidelberg, Germany
Exp Parasitol 101:223-30. 2002
..Treatment of monomorphic bloodstream trypanosomes with pCPTcAMP could be a useful method for identifying the genes involved in the slender-to-stumpy differentiation process...
- Real-time PCR for detection of Trypanosoma brucei in human blood samples
Sven Becker
School of Biological Sciences, University of Bristol, Bristol, United Kingdom
Diagn Microbiol Infect Dis 50:193-9. 2004
..The results indicate that the real-time PCR assay described is a rapid and sensitive method suitable for the detection of T. brucei in human blood samples in routine clinical laboratory practice...
- In vitro effect of DNA topoisomerase inhibitors on Candida albicans
Shing C Kwok
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich
Med Mycol 48:155-60. 2010
..The results of this study indicate that some DNA topoisomerase inhibitors effect the growth and morphology of C. albicans suggesting a possible role as antifungal agents in the treatment of C. albicans infections...
- Impaired dimerization and trafficking of ESAG6 lacking a glycosyl-phosphatidylinositol anchor
Susanne Biebinger
, Im Nevenheimer Feld 282, 69120, Heidelberg, Germany
Mol Biochem Parasitol 132:93-6. 2003
- Screening of acyl hydrazide proteinase inhibitors for antiparasitic activity against Trypanosoma brucei
Conor R Caffrey
Department of Pathology, Tropical Disease Research Unit, University of California San Francisco, San Francisco, CA 94143, USA
Int J Antimicrob Agents 19:227-31. 2002
..Nevertheless, the data support the potential of acyl hydrazides as antitrypanosomal chemotherapeutic agents for treatment of sleeping sickness...
- Bis-acridines as lead antiparasitic agents: structure-activity analysis of a discrete compound library in vitro
Conor R Caffrey
Sandler Center for Basic Research in Parasitic Diseases, BH508, University of California, San Francisco, 1700 4th Street, San Francisco, CA 94158 2330, USA
Antimicrob Agents Chemother 51:2164-72. 2007
..Our approach illustrates the usefulness of screening focused compound libraries against multiple parasite targets. Some of the bis-acridines identified here may represent useful starting points for further lead optimization...
- Intracellular positioning of isoforms explains an unusually large adenylate kinase gene family in the parasite Trypanosoma brucei
Michael L Ginger
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, United Kingdom
J Biol Chem 280:11781-9. 2005
..The anchoring of specific adenylate kinases within two distinct flagellar structures provides a paradigm for metabolic organization and efficiency in other flagellates...
