The unsaturated acyclic nucleoside analogues bearing a sterically constrained ( Z)-4′-benzamido-2′-butenyl moiety: Synthesis, X-ray crystal structure study, cytostatic and antiviral activity evaluations

Abstract

A series of the novel acyclic unsaturated pyrimidine ( 1– 12) and adenine ( 13) nucleoside analogues bearing conformationally restricted ( Z)-2′-butenyl moiety were synthesized and evaluated for their antiviral and cytostatic activity potency against malignant tumor cell lines and normal human fibroblast (WI38). The N-1 and/or N-3 acyclic side chain substitution in pyrimidine ring in N-3 substituted 5-trifluoromethyluracil derivative ( 11), N-1, N-3 disubstituted 5-fluorouracil derivative ( 12) and adenine derivative ( 13) was deduced from their 1H and 13C NMR spectra and confirmed by single crystal X-ray structure analysis. The X-ray crystal structure analysis 11– 13 revealed also supramolecular self-assemblies, in which infinite chains or dimers built two- and three-dimensional networks. The results of the in vitro cytostatic activity evaluations of 1–13 indicate that the majority of the compounds tested exhibited a non-specific and moderate antiproliferative effect at the highest concentration (100 μM). Of all evaluated compounds on the cell lines tested only the N-1 4″-fluoro-substituted-benzamide uracil derivative ( 7) showed rather marked and selective inhibitory activity against the growth of MCF-7 cells at a concentration of 2.7 μM and no cytotoxic effect on normal fibroblasts WI38. This compound can be therefore considered as a potential antitumor lead compound for further synthetic structure modification.