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Studies with the schistosomacide hycanthone: inhibition of macromolecular synthesis and its reversal
Authors:M Wittner  H Tanowitz  R M Rosenbaum
Affiliation:1. Institute of Cognitive Neuroscience and Psychology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Budapest, Hungary;2. János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary;3. Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary;1. Research Centre for Natural Sciences Institute of Cognitive Neuroscience and Psychology, Clinical and Developmental Neuropsychology Research Group, Magyar Tudósok körútja 2., H-1117 Budapest, Hungary;2. Department of Cognitive Science, Faculty of Natural Sciences, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary;3. Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Tűzoltó utca 37-47., H-1094 Budapest, Hungary;4. Integrative Neuroscience Research Group, Institute of Cognitive Neuroscience and Psychology, Research Centre for Natural Sciences, Magyar Tudósok körútja 2., H-1117 Budapest, Hungary;5. Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter utca 50/A., H-1083 Budapest, Hungary;6. Doctoral School of Mental Health Sciences, Semmelweis University, Balassa u. 6., 1083 Budapest, Hungary;8. Department of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, Balassa u. 6., H-1083 Budapest, Hungary
Abstract:The new schistosomacide, hycanthone, was studied with regard to its effects upon macromolecular synthesis in mammalian (HeLa) cells. At concentrations as low as 5 × 10−8M, hycanthone reduces plating efficiency of HeLa cells. At 10−6M, effects on population growth are evident by the second generation. At 5 × 10−6M, RNA synthesis is markedly depressed while DNA and protein synthesis are relatively unaffected. New ribosomal RNA synthesis is rapidly inhibited by hycanthone at 5 × 10−6M, and its processing is markedly delayed. During hycanthone inhibition 28S RNA does not appear in the cytoplasm. Hycanthone inhibition was shown to be readily reversible by washing the cells in fresh medium. The case with which inhibition can be reversed in vitro suggests that it may be necessary to maintain blood levels of this compound if permanent eradication of schistosomal infection is to be attained. Further work must be done to establish this point.
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