Discovery of a potential therapeutic target to combat trypanosomes

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(CNRS) Using cryo-electron microscopy, French researchers at the Institut de Biologie Mol é culaire et Cellulaire (CNRS/Universit é de Strasbourg) have analyzed the structure of trypanosomes parasites in details and revealed one of their potential weak points, which has remained undetected until now. This discovery opens the path to the development of new safer therapies that are less toxic and more specific against trypanosomes, the parasites causing the Chagas disease and the African sleeping sickness.

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Wow – we received so many excellent comments on how parasites and the number 5 go together! Here are many of them – in no particular order – for your viewing pleasure:Pentatrichomonas hominis is a nonpathogenic intestinal flagellate named for its 5 flagella (penta from the Greek pente, meaning five + trich, pertaining to hair [flagella]). By Neil Anderson and Bernardino Rocha.There are 5 lobes of the lung, and all can be infected by Paragonimusspecies. By Brian Duresko.The are 5Plasmodiumspecies that are responsible for the bulk of malaria in humans:P. falciparum, P. vivax, P. ovale, P. malariae, andP. knowlesi(t…

Publication date: Available online 29 July 2019Source: Biochimica et Biophysica Acta (BBA) – Molecular Cell ResearchAuthor(s): Vishal C. Kalel, Mengqiao Li, Stefan Gaussmann, Florent Delhommel, Ann-Britt Schäfer, Bettina Tippler, Martin Jung, Renate Maier, Silke Oeljeklaus, Wolfgang Schliebs, Bettina Warscheid, Michael Sattler, Ralf ErdmannAbstractTrypanosomatid parasites cause devastating African sleeping sickness, Chagas disease, and Leishmaniasis that affect about 18 million people worldwide. Recently, we showed that the biogenesis of glycosomes could be the “Achilles’ heel” of trypanosomatids suitable …

Abstract
More than 10 million people around the world are afflicted by Neglected Tropical Diseases, such as Chagas Disease, Human African trypanosomiasis, and Leishmania. These diseases mostly occur in undeveloped countries that suffer from a lack of economic incentive, research, and policy for new compound development. Sulfonamide moieties are effective scaffolds present in several compounds that are determinants to treat various diseases, principally neglected tropical diseases This review article examines the contribution of these scaffolds in medicinal chemistry in the last five years, focusing on three trypan…

Source: Medicinal ChemistryCategory: Chemistry Authors: Tags: Med Chem Source Type: research

Dalton Trans., 2019, Accepted Manuscript DOI: 10.1039/C9DT01317B, PaperEsteban Rodriguez Arce, Eugenia Putzu, Michel Lapier, Juan Diego Maya, Claudio Olea-Azar, Gustavo Etcheverria, Oscar E. Piro, Andrea Medeiros, Florencia Sardi, Marcelo Comini, Gast ón Risi, Gustavo Salinas, Isabel Correia, João Pessoa, Lucía Otero, Dinorah Gambino In the search for a more effective chemotherapy for the treatment of Chagas disease and Human African trypanosomiasis, caused by Trypanosoma cruzi and Trypanosoma brucei parasites, respectively, the use of… The content of this RSS Feed (c) The Royal Society of Chemistry

Life scientists from UCLA and the University of Bern have identified a key gene in the transmission of African sleeping sickness — a severe disease transmitted by the bite of infected tsetse flies, which are common in sub-Saharan Africa.The disease is fatal if untreated, as the parasite responsible moves from the bloodstream to the central nervous system. Tens of millions of people in 36 African countries are at risk. There is no vaccine, and conventional drug treatments, which include an arsenic derivative, are antiquated, not very effective and have severe side effects.The research,  published in the journal N…

This study aimed to contribute to the need of finding new and more effective bioactive molecules against several of the earlier mentioned threats faced by human kind nowadays. For this, eighteen species from the Actinomycetales previously isolated from Erylus spp. sponges collected in Portuguese marine waters (Açores, Madeira, and continental shelf) were screened for antimicrobial, anti-cancer, anti-parasitic and anti-obesogenic activities.
Materials and Methods
Biological Material
The bacteria under study belong to the order Actinomycetales within the phylum Actinobacteria and were isolated from marine sponges o…

Abstract Neglected Tropical Diseases (NTDs) comprise of a group of seventeen infectious conditions endemic in many developing countries. Among these diseases are three of protozoan origin, namely leishmaniasis, Chagas disease, and African trypanosomiasis, caused by the parasites Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei respectively. These diseases have their own unique challenges which are associated with the development of effective prevention and treatment methods. Collectively, these parasitic diseases cause more deaths worldwide than all other NTDs combined. Moreover, many current therapies for these …

Polyamines are polycationic organic amines that are required for all eukaryotic life, exemplified by the polyamine spermidine, which plays an essential role in translation. They also play more specialized roles that differ across species, and their chemical versatility has been fully exploited during the evolution of protozoan pathogens. These eukaryotic pathogens, which cause some of the most globally widespread infectious diseases, have acquired species-specific polyamine-derived metabolites with essential cellular functions and have evolved unique mechanisms that regulate their core polyamine biosynthetic pathways. Many…

Source: Journal of Biological ChemistryCategory: Chemistry Authors: Tags: Thematic Minireviews Source Type: research

by Lori Ferrins, Amrita Sharma, Sarah M. Thomas, Naimee Mehta, Jessey Erath, Scott Tanghe, Susan E. Leed, Ana Rodriguez, Kojo Mensa-Wilmot, Richard J. Sciotti, Kirsten Gillingwater, Michael P. Pollastri

We recently reported the medicinal chemistry re-optimization of a series of compounds derived from the human tyrosine kinase inhibitor, lapatinib, for activity againstPlasmodium falciparum. From this same library of compounds, we now report potent compounds againstTrypanosoma brucei brucei (which causes human African trypanosomiasis),T.cruzi (the pathogen that causes Chagas disease), andLeishmania spp. (which cause leishma…

This study elucidates the structure and function of l-threonine-3-dehydrogenase (TDH) from T. brucei, the causative pathogen of HAT. TDH is a key enzyme in the metabolism of l-threonine, and an inhibitor of TDH has been shown to have trypanocidal activity in the procyclic form of T. brucei. TDH is a nonfunctional pseudogene in humans, suggesting that it may be possible to rationally design safe and specific therapies for trypanosomiasis by targeting this parasite enzyme. As an initial step, the TDH gene from T. brucei was expressed and the three-dimensional structure of the enzyme was solved by X-ray crystallography. In mu…

Source: Acta Crystallographica Section DCategory: Biochemistry Authors: Tags: protein crystallography structural biology threonine metabolism trypanosomiasis geometric simulations research papers Source Type: research



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