2. Academic Validation
  3. Synthesis, cytostatic and anti-HIV evaluations of the new unsaturated acyclic C-5 pyrimidine nucleoside analogues

Synthesis, cytostatic and anti-HIV evaluations of the new unsaturated acyclic C-5 pyrimidine nucleoside analogues

  • Bioorg Med Chem. 2008 May 15;16(10):5624-34. doi: 10.1016/j.bmc.2008.03.074.
Tatjana Gazivoda 1,  Silvana Raić-Malić,  Vedran Kristafor,  Damjan Makuc,  Janez Plavec,  Sinisa Bratulić,  Sandra Kraljević-Pavelić,  Kresimir Pavelić,  Lieve Naesens,  Graciela Andrei,  Robert Snoeck,  Jan Balzarini,  Mladen Mintas
Affiliations

Affiliation

  • 1 Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, Croatia.
PMID: 18424155 DOI: 10.1016/j.bmc.2008.03.074
Abstract

A series of the novel C-5 alkynyl pyrimidine nucleoside analogues (1-14) in which the sugar moiety was replaced by the conformationally restricted Z- and E-2-butenyl spacer between the phthalimido and pyrimidine ring were synthesized by using Sonogashira cross-coupling reaction. Cytostatic activity evaluation of the novel compounds showed that E-isomers exhibited, in general, better cytostatic activities than the corresponding Z-isomers. E-isomer 14 exhibited the best cytostatic effect against all evaluated malignant cell lines, particularly against hepatocellular carcinoma (Hep G2, IC(50)=4.3microM). However, this compound was also cytotoxic to human normal fibroblasts (WI 38). Its Z-isomer 7 showed highly specific antiproliferative activity against Hep G2 (IC(50)=18microM) and no cytotoxicity to WI 38. Moreover, compounds 3, 4 and 14 expressed some marginal inhibitory activity against HIV-1 and HIV-2.

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