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Gene therapy (suicide gene therapy) is a method which uses herpes simplex virus thymidine kinase (HSV-1 TK) and prodrug (ganciclovir-GCV) combination for the treatment of cancer. That approach has been succesfully applied for the treatment of bone marrow transplantation and for patients who developed lymphomas. However, one of the limitations of this method is ganciclovir resistance to cytomegalovirus infections that frequently occur in allo-BMT patients. The main goal of this study is to synthesize the new acyclic nucleosides as prodrugs which could find a succesful application in gene therapy of cancer. It was found that acyclic nucleoside analogues with 9-(2-hydroxypropyl) and 9-(2-hydroxyetoxymethyl) side chain act as fraudulent substrates for HSV-1 TK. Therefore, the new acyclic nucleoside derivatives (A and B) were synthesized. The novel compounds were evaluated against: murine leukemia (L1210/0), murine mammary carcinoma (FM3A) and human T-lymphocytes (Molt4/C8 and CEM/0). Acetylated acyclic nucleosides containing iodine and chlorine in the positions 2 and 6, respectively, exhibit marked inhibitory effects against malignant tumor cell lines: L1210/0, Molt4/C8 and CEM/0. [1] P. Pospisil, B. D. Pilger, P. Schelling, C. Wurth, L. Scapozza, G. Folkers, M. Pongracic, M. Mintas and S. Raic-Malic, Helv. Chim. Acta, 2002 (85) 3237-3250 |
