DDC- and 3TC-bis(SATE) Monophosphate Prodrugs Overcome Cellular Resistance Mechanisms to HIV-1 Associated with Cytidine Kinase Deficiency |
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| Authors: | B. Gröschel N. Himmel J. Cinatl C. Périgaud G. Gosselin J-L. Imbach |
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| Affiliation: | 1. Institute of Medical Virology, Johann Wolfgang Goethe University Frankfurt/M. , Sandhofstraβe 2-4, 60528, Frankfurt/M., Germany;2. Institute of Medical Virology, Johann Wolfgang Goethe University Frankfurt/M. , Sandhofstraβe 2-4, 60528, Frankfurt/M., Germany;3. Center of Pediatrics, Department of Hematology and Oncology , Johann Wolfgang Goethe University , Frankfurt/M., Germany;4. Laboratoire de Chimie Bioorganique , Université Montpellier II , 34095, Montpellier Cedex 5, France |
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| Abstract: | Abstract A 2,3′-dideoxycytidine (ddC)-resistant T-lymphoid cell line (MOLT-4/8rddC250), in which deoxycytidine kinase (dCK) gene-expression was decreased when compared with parental cells, has been selected. Cytotoxic and antiretroviral activity of ddC and 3TC was significantly lower in MOLT-4/8rddC250 than in parental MOLT-4/8 cells. ddC- and 3TC-bis(SATE)phosphotriesters completely overcame cellular resistance mechanisms and showed comparable both cytotoxic and antiretroviral activity in parental and ddC-resistant cells. |
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