Synthesis and detailed biological testing of thiazole C-nucleozides

Abstract

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

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