We report herein the synthesis and biol. evaluation of novel deoxynucleoside-bile acid conjugates linked through a 1,2,3-triazole ring. The conjugates were synthesized via Cu(i) mediated 1,3-dipolar cycloaddn. reaction ('click' chem.) of 3-azido bile acid derivs. and terminal alkyne moieties linked to the C-8 position of deoxyadenosine. All novel mols. were evaluated in vitro for their anti-proliferative activity against four human cell lines (i.e., leukemic T Jurkat and K562; colon carcinoma HCT116; and ovarian cancer A2780) and their cytotoxicity toward human fibroblast cells. Several conjugates exhibited strong anti-proliferative activity against human leukemia T cells. The best cytotoxicity was obsd. for HdA-CDC on both leukemia cell lines with IC50 up to 8.51 μM. The apoptotic activity of several conjugates was also established.
Synthesis and in vitro cytotoxicity of deoxyadenosine-bile acid conjugates linked with 1,2,3-triazole
PERRONE, Daniela;BORTOLINI, Olga;FOGAGNOLO, Marco;MARCHESI, Elena;MARI, Lara;MASSARENTI, Chiara;SFORZA, Fabio;VARANI, Katia;
2013
Abstract
We report herein the synthesis and biol. evaluation of novel deoxynucleoside-bile acid conjugates linked through a 1,2,3-triazole ring. The conjugates were synthesized via Cu(i) mediated 1,3-dipolar cycloaddn. reaction ('click' chem.) of 3-azido bile acid derivs. and terminal alkyne moieties linked to the C-8 position of deoxyadenosine. All novel mols. were evaluated in vitro for their anti-proliferative activity against four human cell lines (i.e., leukemic T Jurkat and K562; colon carcinoma HCT116; and ovarian cancer A2780) and their cytotoxicity toward human fibroblast cells. Several conjugates exhibited strong anti-proliferative activity against human leukemia T cells. The best cytotoxicity was obsd. for HdA-CDC on both leukemia cell lines with IC50 up to 8.51 μM. The apoptotic activity of several conjugates was also established.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
