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American trypanosomiasis

Karina Vázquez, Margot Paulino, Cristian O Salas, Juan J Zarate-Ramos, Brenda Vera, Gildardo Rivera
Chagas disease or American trypanosomiasis is a major parasitic disease in Latin America with treatment available via two drugs: nifurtimox and benznidazole. These two treatments are ineffective in the chronic phase of the disease. Therefore, there is a need for the development of new, efficient and safe drugs for the treatment of these diseases. With this goal, one of the promising targets proposed is the trypanothione reductase (TR), a key enzyme important in the metabolism of Trypanosoma cruzi. In this review, we analyze the importance of TR as a drug target, as well as their compounds inhibitors reported in the last decade as potential therapeutic agents for Chagas disease...
March 15, 2017: Mini Reviews in Medicinal Chemistry
Luisa Berná, Maria Laura Chiribao, Gonzalo Greif, Matias Rodriguez, Fernando Alvarez-Valin, Carlos Robello
American trypanosomiasis is a chronic and endemic disease which affects millions of people. Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages of T. cruzi: amastigotes, epimastigotes and trypomastigotes...
2017: PeerJ
Esteban Rodríguez Arce, Ignacio Machado, Belén Rodríguez, Michel Lapier, María Carolina Zúñiga, Juan Diego Maya, Claudio Olea Azar, Lucía Otero, Dinorah Gambino
American Trypanosomiasis is a chronic infection discovered and described in 1909 by the Brazilian scientist Carlos Chagas. It is caused by the protozoan parasite Trypanosoma cruzi. Although it affects about 10million people in Latin America, the current chemotherapy is still inadequate. The discovery of new drugs is urgently needed. Our group is focused on the development of prospective metal-based drugs mainly based on bioactive ligands and pharmacologically interesting metal ions. In this work three new rhenium(I) tricarbonyl compounds fac-[Re(I)(CO)3Br(HL)] where HL=5-nitrofuryl containing thiosemicarbazones were synthesized and fully characterized in solution and in the solid state...
January 23, 2017: Journal of Inorganic Biochemistry
Camila Piva Abegg, Ana Paula de Abreu, Juliane Lopes da Silva, Silvana Marques de Araújo, Mônica Lúcia Gomes, Érika Cristina Ferreira, Max Jean de Ornelas Toledo
Trypanosoma cruzi is the etiologic agent of American trypanosomiasis has broad biological and genetic diversity. Remaining to be studied are polymorphisms of the blood forms and metacyclogenesis of different T. cruzi discrete typing units (DTUs). Our goal was to evaluate the relationship between T. cruzi DTUs, the morphology of blood trypomastigotes, and in vitro metacyclogenesis. T. cruzi strains that pertained to DTUs TcI, TcII, and TcIV from different Brazilian states were used. Parameters that were related to the morphology of eight strains were assessed in thin blood smears that were obtained from mice that were inoculated with blood or culture forms, depending on strain...
May 2017: Experimental Parasitology
Karla Fabiola Chacón-Vargas, Benjamin Nogueda-Torres, Luvia E Sánchez-Torres, Erick Suarez-Contreras, Juan Carlos Villalobos-Rocha, Yuridia Torres-Martinez, Edgar E Lara-Ramirez, Giulia Fiorani, R Luise Krauth-Siegel, Maria Laura Bolognesi, Antonio Monge, Gildardo Rivera
Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59...
February 1, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Eric Chatelain
Chagas disease, or American trypanosomiasis, is the result of infection by the parasite Trypanosoma cruzi. It is endemic in Latin America, and spreading around the globe due to human migration. Although it was first identified more than a century ago, only two old drugs are available for treatment and a lot of questions related to the disease progression, its pathologies, and not to mention the assessment of treatment efficacy, are subject to debate and remain to be answered. Indeed, the current status of evidence and data available does not allow any absolute statement related to treatment needs and outcome for Chagas patients to be made...
2017: Computational and Structural Biotechnology Journal
Rafael Hernán Navarrete-Sandoval, Maximiliano Servín-Rojas
BACKGROUND Chagas disease is a chronic parasitosis transmitted by the inoculation of infected triatomine feces into wounds or conjunctival sac, transfusion, congenitally, organ transplantation, and ingestion of contaminated food. The disease is classified into an acute and chronic phase; the latter is a life-long infection that can be asymptomatic or progress to cardiac or digestive complications. CASE REPORT We report a case of acute-phase Chagas disease, transmitted by the splash of gut content from an infected triatomine into the conjunctival mucosa...
December 29, 2016: American Journal of Case Reports
Ana Paula Margioto Teston, Ana Paula de Abreu, Camila Piva Abegg, Mônica Lúcia Gomes, Max Jean de Ornelas Toledo
A new epidemiological view of American trypanosomiasis or Chagas disease has been formulated in recent decades. Oral transmission of the etiological agent of Chagas disease, Trypanosoma cruzi, has been the most common form of transmission. The T. cruzi discrete typing units TcI and TcIV have been involved in tens outbreaks of acute cases of Chagas disease in the Brazilian Amazon region. We investigated the intensity of infection in mice that were orally inoculated (OR group) with four strains of TcIV that were isolated from two outbreaks of acute Chagas disease that was orally acquired in the state of Amazonas, Brazil...
February 2017: Acta Tropica
Rola M Labib, Sherif S Ebada, Fadia S Youssef, Mohamed L Ashour, Samir A Ross
BACKGROUND: Leishmaniasis and African trypanosomiasis are recognized as the leading causes of mortality and morbidity with the greatest prevalence in the developing countries. They affect more than one billion of the poorest people on the globe. OBJECTIVE: To find a cheap, affordable, safe, and efficacious antileshmanial and antitrypanosomal natural drug and to elucidate its probable mode of action. MATERIALS AND METHODS: Phytochemical investigation of the non-polar fraction of the methanol extract of leaves of Ochrosia elliptica Labill...
October 2016: Pharmacognosy Magazine
Taliha Dias Perez, Fabiano Borges Figueiredo, Artur Augusto Mendes Velho Junior, Valmir Laurentino Silva, Maria de Fátima Madeira, Reginaldo Peçanha Brazil, José Rodrigues Coura
Chagas disease and the leishmaniases are endemic zoonoses of great importance to public health in the state of Piauí, Brazil. The domestic dog (Canis familiaris) is a major reservoir, host of Trypanosoma cruzi and Leishmania spp. in both urban and rural areas, playing an important role in the transmission of these parasites. The present study evaluated the prevalence of both infectious diseases in dogs of a rural area in the municipality of São João do Piauí, Piauí State. One hundred twenty-nine blood samples were collected for serological assessment: for the leishmaniases, 49 (38%) animals tested positive by the Dual-Path Platform technology (DPP), nine (6%) by the Enzyme-linked Immunosorbent Assay (ELISA), and 19 (14...
November 3, 2016: Revista do Instituto de Medicina Tropical de São Paulo
Vilma G Duschak
BACKGROUND: The American trypanosomiasis, Chagas disease, is a parasitic infection typically spread by triatomine vectors affecting millions of people all over Latin America. Existing chemotherapy is centered on the nitroaromatic compounds benznidazole and nifurtimox that provide unsatisfactory results and substantial side effects. So, the finding and exploration of novel ways to challenge this neglected disease is a main priority. METHODS: The biologic and biochemical progress in the scientific knowledge of Trypanosoma cruzi in the period comprising last 15-years has increased the identification of multiple targets for Chagas´ disease chemotherapy...
2016: Recent Patents on Anti-infective Drug Discovery
Vanessa Bellini Bardella, Sebastián Pita, André Luis Laforga Vanzela, Cleber Galvão, Francisco Panzera
The subfamily Triatominae (Hemiptera, Reduviidae) includes 150 species of blood-sucking insects, vectors of Chagas disease or American trypanosomiasis. Karyotypic information reveals a striking stability in the number of autosomes. However, this group shows substantial variability in genome size, the amount and distribution of C-heterochromatin, and the chromosome positions of 45S rDNA clusters. Here, we analysed the karyotypes of 41 species from six different genera with C-fluorescence banding in order to evaluate the base-pair richness of heterochromatic regions...
October 2016: Memórias do Instituto Oswaldo Cruz
C Díaz-Luján, M F Triquell, C Castillo, D Hardisson, U Kemmerling, R E Fretes
American trypanosomiasis has long been a neglected disease endemic in LatinAmerica, but congenital transmission has now spread Chagas disease to cause a global health problem. As the early stages of the infection of placental tissue and the vertical transmission by Trypanosoma cruzi are still not well understood, it is important to investigate the relevance of the first structure of the placental barrier in chorionic villi infection by T. cruzi during the initial stage of the infection. Explants of human chorionic villi from healthy pregnant women at term were denuded of their syncytiotrophoblast and co-cultured for 3h, 24h and 96h with 800,000 trypomastigotes (simulating acute infection)...
December 2016: Acta Tropica
Isidro Jarque, Miguel Salavert, Javier Pemán
Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients...
2016: Mediterranean Journal of Hematology and Infectious Diseases
Juan B Rodriguez, Bruno N Falcone, Sergio H Szajnman
INTRODUCTION: Trypanosoma cruzi is the etiologic agent of American trypanosomiasis (Chagas disease), which is one of the important parasitic diseases worldwide. The number of infected people with T. cruzi diminished from 18 million in 1991 to 6 million in 2010, but it is still the most prevalent parasitic disease in the Americas. The existing chemotherapy is still deficient and based on two drugs: nifurtimox and benznidazole, which are not FDA-approved in the United States. AREAS COVERED: This review covers the current and future directions of Chagas disease chemotherapy based on drugs that interfere with relevant metabolic pathways...
September 2016: Expert Opinion on Therapeutic Patents
Kiyosei Takasu
The search for new drugs that could treat tropical protozoan diseases, such as malaria or neglected tropical diseases (NTDs), motivates many medicinal chemists. New classes of antiprotozoal drugs that act through a novel mechanism of action must be developed. This review presents our efforts toward finding new candidate treatments for malaria, American trypanosomiasis, human African trypanosomiasis and leishmaniasis based on π-delocalized lipophilic cations (DLCs). DLCs, such as rhodacyanines, azarhodacyanines, β-carbolinium salts, and phenoxazinium salts, displayed strong antiprotozoal activities with highly selective indices...
2016: Chemical & Pharmaceutical Bulletin
Rocio Paucar, Elsa Moreno-Viguri, Silvia Pérez-Silanes
Chagas disease or American trypanosomiasis is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Although the number of infected individuals has decreased, about 6-7 million people are infected worldwide. The chemotherapy drugs currently used are limited to benznidazole and nifurtimox. They are effective in acute phase, congenital transmission and children with chronic infection; however, recent clinical trials have shown limitations in adults with chronic infection, presenting drawbacks during the treatment...
2016: Current Medicinal Chemistry
F Chacón, A Bacigalupo, J F Quiroga, A Ferreira, P E Cattan, G Ramírez-Toloza
American trypanosomiasis is a chronic disease transmitted mainly by vectors. The hematophagous triatomine vectors transmit Trypanosoma cruzi to a wide variety of mammals, which usually are their food source. This study determined the feeding profile of Mepraia spinolai, a sylvatic triatomine vector, present in endemic areas of Chile. Vectors were captured in the north-central area of Chile. Samples of intestinal contents were analyzed by an Enzyme-linked immunosorbent assay (ELISA) that identifies and discriminates the presence of serum antigens from Homo sapiens and nine animal species (Canis familiaris, Felis catus, Capra hircus, Mus musculus, Gallus gallus, Octodon degus, Thylamys elegans, Phyllotis darwini and Oryctolagus cuniculus)...
October 2016: Acta Tropica
Charles O Ogindo, Mozna H Khraiwesh, Matthew George, Yakini Brandy, Nailah Brandy, Ayele Gugssa, Mohammad Ashraf, Muneer Abbas, William M Southerland, Clarence M Lee, Oladapo Bakare, Yayin Fang
Chagas disease, also called American trypanosomiasis, is a parasitic disease caused by Trypanosoma cruzi (T. cruzi). Recent findings have underscored the abundance of the causative organism, (T. cruzi), especially in the southern tier states of the US and the risk burden for the rural farming communities there. Due to a lack of safe and effective drugs, there is an urgent need for novel therapeutic options for treating Chagas disease. We report here our first scientific effort to pursue a novel drug design for treating Chagas disease via the targeting of T...
August 15, 2016: Bioorganic & Medicinal Chemistry
Juan Bautista Rodriguez
Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3β-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas disease. These metabolites are crucial; consequently, the enzymes implicated in catalyzing their formation constitute interesting molecular targets for drug design...
2016: Mini Reviews in Medicinal Chemistry
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