scholarly journals A targeted delivery strategy for the development of potent trypanocides

2017 ◽  
Vol 53 (62) ◽  
pp. 8735-8738 ◽  
Author(s):  
Heeren M. Gordhan ◽  
Jillian E. Milanes ◽  
Yijian Qiu ◽  
Jennifer E. Golden ◽  
Kenneth A. Christensen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Trypanosoma Brucei ◽  
Causative Agent ◽  
Targeted Delivery ◽  
Sleeping Sickness ◽  
African Sleeping Sickness ◽  
Delivery Strategy ◽  
New Drug

A new drug delivery strategy was investigated for the development of potent anti-parasitic compounds againstTrypanosoma brucei, the causative agent of African sleeping sickness.

scholarly journals Inhibitors Incorporating Zinc‐Binding Groups Target the GlcNAc‐PI de‐ N ‐acetylase in Trypanosoma brucei , the Causative Agent of African Sleeping Sickness

2012 ◽  
Vol 79 (3) ◽  
pp. 270-278 ◽  
Author(s):  
Nuha Z. Abdelwahab ◽  
Arthur T. Crossman ◽  
Lauren Sullivan ◽  
Michael A. J. Ferguson ◽  
Michael D. Urbaniak
Keyword(s):  
Trypanosoma Brucei ◽  
Causative Agent ◽  
Sleeping Sickness ◽  
Zinc Binding ◽  
African Sleeping Sickness

scholarly journals T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6099
Author(s):  
Lee J. Silverberg ◽  
Tapas K. Mal ◽  
Carlos N. Pacheco ◽  
Megan L. Povelones ◽  
Madeline F. Malfara ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Trypanosoma Brucei ◽  
Causative Agent ◽  
Room Temperature ◽  
Sleeping Sickness ◽  
African Sleeping Sickness ◽  
Specialized Equipment ◽  
Ready Access ◽  
Phenyl Compounds ◽  
Kinetoplastid Parasite

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.

scholarly journals Novel Cytoskeleton-Associated Proteins in Trypanosoma brucei Are Essential for Cell Morphogenesis and Cytokinesis

2021 ◽  
Vol 9 (11) ◽  
pp. 2234
Author(s):  
Marina Schock ◽  
Steffen Schmidt ◽  
Klaus Ersfeld
Keyword(s):  
Trypanosoma Brucei ◽  
Causative Agent ◽  
Sleeping Sickness ◽  
Cytoskeletal Proteins ◽  
Cell Morphogenesis ◽  
Proteomics Data ◽  
Microtubule Cytoskeleton ◽  
African Sleeping Sickness ◽  
Associated Proteins ◽  
Cellular Integrity

Trypanosome brucei, the causative agent of African sleeping sickness, harbours a highly ordered, subpellicular microtubule cytoskeleton that defines many aspects of morphology, motility and virulence. This array of microtubules is associated with a large number of proteins involved in its regulation. Employing proximity-dependent biotinylation assay (BioID) using the well characterised cytoskeleton-associated protein CAP5.5 as a probe, we identified CAP50 (Tb927.11.2610). This protein colocalises with the subpellicular cytoskeleton microtubules but not with the flagellum. Depletion by RNAi results in defects in cytokinesis, morphology and partial disorganisation of microtubule arrays. Published proteomics data indicate a possible association of CAP50 with two other, yet uncharacterised, cytoskeletal proteins, CAP52 (Tb927.6.5070) and CAP42 (Tb927.4.1300), which were therefore included in our analysis. We show that their depletion causes phenotypes similar to those described for CAP50 and that they are essential for cellular integrity.

scholarly journals The tRNA Methylome of Trypanosoma brucei , the Causative Agent of African Sleeping Sickness

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Justine Lazatin ◽  
Leanne Chen ◽  
Sarah Ackerman ◽  
Jie Wang ◽  
Erika Valentine ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Causative Agent ◽  
Sleeping Sickness ◽  
African Sleeping Sickness

scholarly journals The Molecular Dynamics of Trypanosoma brucei UDP‐Galactose 4′‐Epimerase: A Drug Target for African Sleeping Sickness

2012 ◽  
Vol 80 (2) ◽  
pp. 173-181 ◽  
Author(s):  
Aaron J. Friedman ◽  
Jacob D. Durrant ◽  
Levi C. T. Pierce ◽  
Thomas J. McCorvie ◽  
David J. Timson ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Trypanosoma Brucei ◽  
Drug Target ◽  
Sleeping Sickness ◽  
African Sleeping Sickness

scholarly journals A global sensitivity analysis for African sleeping sickness

Parasitology ◽  
2010 ◽  
Vol 138 (4) ◽  
pp. 516-526 ◽  
Author(s):  
STEPHEN DAVIS ◽  
SERAP AKSOY ◽  
ALISON GALVANI
Keyword(s):  
Trypanosoma Brucei ◽  
Control Strategies ◽  
Sleeping Sickness ◽  
Sensitivity Analyses ◽  
Tsetse Flies ◽  
East African ◽  
African Sleeping Sickness ◽  
Regular Treatment ◽  
Global Sensitivity ◽  
Parameter Ranges

SUMMARYAfrican sleeping sickness is a parasitic disease transmitted through the bites of tsetse flies of the genus Glossina. We constructed mechanistic models for the basic reproduction number, R0, of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively the causative agents of West and East African human sleeping sickness. We present global sensitivity analyses of these models that rank the importance of the biological parameters that may explain variation in R0, using parameter ranges based on literature, field data and expertize out of Uganda. For West African sleeping sickness, our results indicate that the proportion of bloodmeals taken from humans by Glossina fuscipes fuscipes is the most important factor, suggesting that differences in the exposure of humans to tsetse are fundamental to the distribution of T. b. gambiense. The second ranked parameter for T. b. gambiense and the highest ranked for T. b. rhodesiense was the proportion of Glossina refractory to infection. This finding underlines the possible implications of recent work showing that nutritionally stressed tsetse are more susceptible to trypanosome infection, and provides broad support for control strategies in development that are aimed at increasing refractoriness in tsetse flies. We note though that for T. b. rhodesiense the population parameters for tsetse – species composition, survival and abundance – were ranked almost as highly as the proportion refractory, and that the model assumed regular treatment of livestock with trypanocides as an established practice in the areas of Uganda experiencing East African sleeping sickness.

scholarly journals Pharmacological Validation of Trypanosoma brucei Phosphodiesterases B1 and B2 as Druggable Targets for African Sleeping Sickness

2011 ◽  
Vol 54 (23) ◽  
pp. 8188-8194 ◽  
Author(s):  
Nicholas D. Bland ◽  
Cuihua Wang ◽  
Craig Tallman ◽  
Alden E. Gustafson ◽  
Zhouxi Wang ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Sleeping Sickness ◽  
African Sleeping Sickness ◽  
Druggable Targets

Screening North American Plant Extracts Against Trypanosoma brucei, a Causative Agent for Sleeping Sickness

Planta Medica ◽  
2011 ◽  
Vol 77 (05) ◽  
Author(s):  
SK Jain ◽  
R Sahu ◽  
V Samoylenko ◽  
M Ilias ◽  
LA Walker ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Causative Agent ◽  
Plant Extracts ◽  
North American ◽  
Sleeping Sickness
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