Synthesis, cytostatic and anti-viral activity evaluation of the novel acyclic nucleoside analogues containing a sterically constrained (Z)-4-amino-2-butenyl moiety
Wittine, Karlo × Benci, Kresimir Pavelic, Sandra Kraljevic Pavelic, Kresimir Bratulic, Sinisa Hock, Karlo Balzarini, Jan Mintas, Mladen #
Medicinal Chemistry Research vol:20 issue:3 pages:280-286
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 x 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 mu M.