Synthesis, cytostatic and anti-viral activity evaluation of the novel acyclic nucleoside analogues containing a sterically constrained (Z)-4-amino-2-butenyl moiety
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A series of the novel pyrimidine (3–6) and purine (12–15, 18–21) acyclic nucleoside analogues in which the sugar moiety was replaced by a sterically constrained Z-4-amino-, 4-aminohydrochloride-2-butenyl, or aliphatic 4-aminohydrochloride-2-butyl moiety were synthesized and evaluated for their anti-viral and cytostatic activity potency. Cytostatic evaluation of the novel compounds on selected panel of human tumour-cell lines showed that the majority of compounds exerted a non-specific anti-proliferative effect at the highest tested concentration (i.e. 1 × 10−4 M) against all cell lines. Nevertheless, a rather moderate but selective anti-proliferative effects on HeLa cell cultures in comparison to normal fibroblasts WI 38, were observed for compounds 15 and 21. No anti-viral activity was observed, except for compounds 3, 4, 5 and 19 that showed anti-HIV activity at 50% effective concentration ranging between 10 and 96 μM.
KeywordsAcyclic nucleoside analogues Purine and pyrimidine derivatives Cytostatic activity Anti-viral activity
Support for this study was provided by the Ministry of Science of the Republic of Croatia (Projects # 125-0982464-2922, # 098-0982464-2393) and by the “Geconcerteerde Onderzoeksacties” of the Katholieke Universiteit Leuven (project # 05/19). We thank Lizette van Berckelaer for excellent technical assistance in performing part of the anti-tumour cell activity assays, as well as Leen Ingels, Leentje Persoons, Frieda De Meyer, Vicky Broeckx, Anita Camps and Lies Vandenheurck for excellent technical assistance in performing the anti-viral activity assays.
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