Sinteza i detaljna biološka ispitivanja tiazolnih C-nukleozida

Abstract

U radu je ostvarena totalna sinteza novih acikličnih tiazolnih C-nukleozide sa dvostrukom vezom i 2′,3′-dideoksi funkcijom u šećernoj komponenti. Ostvarena višefazna sinteza pomenutih acikličnih analoga tiazofurina zasnovana je na D-arabinozi kao hiralnom prekursoru. Ispitana je in vitro citotoksična aktivnost novosintetizovanih nukleozida prema ćelijskim linijama K562, HL-60, HT-29, MCF-7, MDA-MB-231, HeLa, Raji, PC3, Jurkat, Hs 294T i MRC-5, kao i provera ćelijskih mehanizama koji su u osnovi uočenog citotoksičnog potencijala novosintetisanih analoga u odnosu na tiazofurin kao referentno jedinjenje.

A total synthesis of new acyclic thiazole C-nucleozides bearing a double bond or 2′,3′-dideoxy functionality in the sugar moiety was achieved in this work. The multi-step synthesis of the mentioned thiazofurin analogues is based on D-arabinose as a chiral precursor. In vitro cytotoxic activity of newly synthesized compounds was evaluated against the following cell lines: K562, HL-60, HT-29, MCF-7, MDA-MB-231, HeLa, Raji, PC3, Jurkat, Hs 294T and MRC-5. A study of cell mechanisms underlaying the significant cytotoxic potential of these molecules was caried out and the results were compared to thiazofurin that servad as a referent compound in all biological testings.