caa a22 4500 445314338 CHVBK 20180317142641.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s11095-011-0586-3 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0586-3 Mitochondria and Trypanosomatids: Targets and Drugs [Elektronische Daten] [Lianet Fidalgo, Lars Gille] ABSTRACT: The family Trypanosomatidae, flagellated parasitic protozoa, is responsible for important infectious diseases in humans: sleeping sickness, Chagas diseases and leishmaniasis. Currently, development of effective vaccines against these parasites remains an unrealized goal, and clinical management is based on chemotherapeutics. Cost, toxicity and resistance problems of conventional drugs result in an urgent need to identify and develop new therapeutic alternatives. The sound understanding of parasites, biology is key for identifying novel lead structures and new drug targets. This article reviews current knowledge about mitochondrial drug targets and existing drugs against Trypanosoma and Leishmania. In the past, several targets in trypanosomatid mitochondria (electron transport chain, kDNA and topoisomerases, tRNA import and fatty acid synthesis) have been identified. It has been suggested that inhibition of certain targets is involved in triggering apoptosis by impairment of mitochondrial membrane potential and/or production of reactive oxygen species. The inhibitory mechanism of approved drugs, such as pentamidine, nifurtimox, artemisinin and atovaquone, is described in parallel with others products from preclinical studies. In spite of the large amount of genetic information, the analysis of the phenotype of the trypanosomatid mitochondrion in different life stages will remain a useful tool to design new active compounds with selective toxicity against these parasites. Springer Science+Business Media, LLC, 2011 drug nationallicence Leishmania nationallicence mitochondria nationallicence target nationallicence Trypanosoma nationallicence DIM : 3,3′diindolylmethane nationallicence ETC : electron transport chain nationallicence FAS : fatty acid synthesis nationallicence FRD : fumarate reductase nationallicence gRNAs : short transcripts RNA nationallicence HAT : Human African Trypanosomiasis nationallicence kDNA : kinetoplastid DNA nationallicence MMP : mitochondrial membrane potential nationallicence NADH : nicotinamide adenine dinucleotide nationallicence NTDs : neglected tropical diseases nationallicence PCD : programmed cell death nationallicence RIC : rNA import complex nationallicence ROS : reactive oxygen species nationallicence TAO : Trypanosoma alternative oxidase nationallicence tRNA : transcription DNA nationallicence Fidalgo Lianet Departamento de Parasitología, Instituto de Medicina Tropical "Pedro Kourí”, Marianao 13, Apartado Postal No. 601, Ciudad Habana, Cuba aut Gille Lars Institute of Pharmacology and Toxicology Department of Biomedical Sciences, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2758-2770 0724-8741 28:11<2758 2011 28 11095 https://doi.org/10.1007/s11095-011-0586-3 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0586-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fidalgo Lianet Departamento de Parasitología, Instituto de Medicina Tropical "Pedro Kourí”, Marianao 13, Apartado Postal No. 601, Ciudad Habana, Cuba aut NATIONALLICENCE 700 1- Gille Lars Institute of Pharmacology and Toxicology Department of Biomedical Sciences, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2758-2770 0724-8741 28:11<2758 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer