engleski

Synthesis, spectroscopic characterization and biological activity of N-1-sulfonylcytosine derivatives

Large scale preparation of N-1-sulfonylcytosine derivatives has been optimized. The best method was the condensation reaction of silylated cytosine (1) with p-toluenesulfonyl chloride in acetonitrile. Depending on the isolation procedure, 1-(p-toluenesulfonyl)cytosine 2 and 1- (p-toluenesulfonyl)cytosine hydrochloride 3 were isolated in 80 % and 75 % yield, respectively. The NMR evidence presented, shows that 2 appears as a common keto-amino tautomer in DMSO-d6 solution while its hydrochloride 3 forms exclusively rare keto-imino tautomer. N-1-Sulfonylcytosine derivatives 2 and 3 were investigated for possible cytotoxic activity on human normal fibroblasts (WI38), human pancreatic adenocarcinoma cells (MIAPaCa2), poorly differentiated cells from lymph node metastasis of colon carcinoma (SW-620), and human Burkitt lymphoma cells (Raji). MTT- cytotoxicity screens in human tissue culture cell lines showed that both of investigated compounds demonstrated antiproliferative activity in the different histological types of tumors. In comparison with 5-fluorouracil, some of N-1- sulfonylcytosine derivatives showed 10 times stronger activity, considering IC50. The inhibitory effect of the investigated derivatives on normal human cells was lower in comparison to antitumor effects. In addition to the antitumor effects, hematologic findings following the parenteral administration of substances were also investigated.

N-1-Sulfonylcytosine derivatives ; in vitro antiproliferative effect ; antitumor activity ; hematologic findings

Rad je kao poster prezentiran na skupu MMC2004, održanom od 10.-14.06.2004.g., Cavtat, Hrvatska ; uz međunarodnu recenziju objavljen u Knjizi sažetaka ; te na skupu The 19th Dubrovnik International Course & Conference on the Interfaces among Mathematics, Chemistry and Computer Sciences (MATH/CHEM/COMP 2004), održanom od 21-26.06.2004.g., Dubrovnik, Hrvatska, objavljen uz međunarodnu recenziju u Knjizi sažetaka / Ante Graovac, Biserka Pokrić, Vilko Smrečki, ur. ; Zagreb : Ruđer Bošković Institute , 2004.g., str. 32-32.