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Targeting the Trypanosome Alternative Oxidase (TAO) as Promising Chemotherapeutic Approach for African Trypanosomiasis
Christophe Dardonville
* 1 ,
Francisco José Fueyo González
1 ,
Carolina Izquierdo García
1 ,
Teresa Díaz Ayuga
1 ,
Godwin U Ebiloma
2 ,
Emmanuel Balogun
3, 4 ,
Kiyoshi Kita
3, 5 ,
Harry P de Koning
2
1  Instituto de Química Médica, IQM–CSIC, Juan de la Cierva 3, E–28006 Madrid, Spain
2  Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
3  Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Japan
4  Department of Biochemistry, Ahmadu Bello University, Zaria 2222, Nigeria
5  School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, 852-8523, Japan
Published: 01 November 2017 by MDPI in 3rd International Electronic Conference on Medicinal Chemistry session Round Table on Parasitic Diseases
https://doi.org/10.3390/ecmc-3-04641
Abstract:

In Trypanosoma brucei, a parasite that causes African trypanosomiasis in humans (sleeping sickness) and in livestock (nagana) throughout sub-Saharan Africa, the trypanosome alternative oxidase (TAO) is essential for the respiration of bloodstream form parasites (i.e. the human-infective form). Since TAO has no counterpart in mammalian cells and it is conserved among T. brucei subspecies, it has been validated as a promising target for the chemotherapy of African trypanosomiasis.

We present here a successful approach to boost the activity of TAO inhibitors based on the conjugation of the inhibitor with lipophilic cations (LC) that can cross lipid bilayers by non-carrier mediated transport, and thus accumulate specifically into mitochondria, driven by the plasma and mitochondrial transmembrane potentials (negative inside). This design afforded several LC–TAO inhibitor conjugates active in the submicromolar to low nanomolar range against wild type and resistant strains of African trypanosomes (T. b. brucei, T. congolense), with selectivity over human cells >500.

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Comments on this paper
Smith Stone
13 September 2018
Nice info
Sleeping sickness or African trypanosomiasis is a parasitic malady in individuals and creatures, caused by protozoa of the sort Trypanosoma and transmitted by the tsetse fly. Essay Writer Service. The sickness is endemic in specific locales of Sub-Saharan Africa, covering around 36 nations and 60 million individuals. It is assessed that 50,000 to 70,000 individuals are right now contaminated, the number has declined to some degree lately.


 
 
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