Naslov
Synthesis, X-ray crystal structural study, antiviral and cytostatic evaluations of the novel unsaturated acyclic and epoxide nucleoside analogues

Autori
Krištafor, Vedran ; Raić-Malić, Silvana ; Cetina, Mario ; Kralj, Marijeta ; Šuman, Lidija ; Pavelić, Krešimir ; Balzarini, Jan ; De Clercq, Erik ; Mintas, Mladen

Izvornik
Bioorganic & medicinal chemistry (0968-0896) 14 (2006), 23; 8126-8138

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
olephinic nucleoside analogues ; epoxide purine derivatives ; cytostytic activity ; anti-HIV-1 activity

Sažetak
A series of the novel purine and pyrimidine nucleoside analogues were synthesised in which the sugar moiety was replaced by the 4-amino-2-butenyl (2-6 and 10-18) and oxiranyl (8 and 20) spacer. Novel Z- (2-6) and E-isomers (10-18) of unsaturated acyclic nucleoside analogues were synthesized by condensation of 2- and 6-substituted purine and 5-substituted uracil bases with Z- (1) or E-phthalimide (9) precursors. The oxiranyl nucleoside analogues (8 and 20) were obtained by epoxidation of 1 and 9 with m-chloroperoxybenzoic acid and subsequent coupling with adenine. All the novel compounds were evaluated for their antiviral and antitumor cell activities. Among the olefinic nucleoside analogues, Z-isomer of adenine containing 4-amino-2-butenyl side chain (6) exhibited the best cytostatic activities, particularly against colon carcinoma (SW 620, IC50 = 26 uM). Its E-isomer 15 did not show any antiprolipherative activity against malignant tumor cell lines, except for a slight inhibition of colon carcinoma (SW 620, IC50 = 56.5 uM) cells. In general, Z-isomers showed better cytostatic activities than the corresponding E-isomers. (Z)-4-Amino-2-butenyl-adenine nucleoside analogue 6 showed albeit modest but selective activity against HIV-1 (EC50 = 4.83 ugmL-1).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA