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Transforming the chemotherapy of human African trypanosomiasis.
Clin Microbiol Rev
January 2025
School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
SUMMARYPrior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement.
View Article and Find Full Text PDFEflornithine for treatment of high-risk neuroblastoma.
Trends Pharmacol Sci
June 2024
Department of Pharmaceutical Sciences, Department of Anatomy and Neurobiology, Drug Discovery Center, Neuroscience Institute, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address:
Identification of transport systems involved in eflornithine delivery across the blood-brain barrier.
Front Drug Deliv
May 2023
King's College London, Institute of Pharmaceutical Science, Franklin-Wilkins Building, Stamford Street, London, UK.
Human African Trypanosomiasis (HAT) is a neglected parasitic disease that continues to persist in sub-Saharan Africa. It is fatal if untreated. The first stage of the disease is associated with the presence of the parasite in the periphery and the second stage with the presence of the parasites in the CNS.
View Article and Find Full Text PDFInsights to Design New Drugs against Human African Trypanosomiasis Targeting Rhodesain using Covalent Docking, Molecular Dynamics Simulations, and MM-PBSA Calculations.
Curr Comput Aided Drug Des
December 2024
Postgraduate Program in Pharmaceutical Sciences, State University of Paraíba, Campina Grande, 58429-500, Brazil.
Background: Neglected tropical diseases (NTDs) are parasitic and bacterial diseases that affect approximately 149 countries, mainly the poor population without basic sanitation. Among these, Human African Trypanosomiasis (HAT), known as sleeping sickness, shows alarming data, with treatment based on suramin and pentamidine in the initial phase and melarsoprol and eflornithine in the chronic phase. Thus, to discover new drugs, several studies point to rhodesain as a promising drug target due to the function of protein degradation and intracellular transport of proteins between the insect and host cells and is present in all cycle phases of the parasite.
View Article and Find Full Text PDFPolyamine Metabolism for Drug Intervention in Trypanosomatids.
Pathogens
January 2024
Departamento de Ciencias Biomédicas, Campus de Vegazana s/n, Universidad de León, 24071 León, Spain.
Neglected tropical diseases transmitted by trypanosomatids include three major human scourges that globally affect the world's poorest people: African trypanosomiasis or sleeping sickness, American trypanosomiasis or Chagas disease and different types of leishmaniasis. Different metabolic pathways have been targeted to find antitrypanosomatid drugs, including polyamine metabolism. Since their discovery, the naturally occurring polyamines, putrescine, spermidine and spermine, have been considered important metabolites involved in cell growth.
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