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

Kašnar-Šamprec, Jelena; Glavaš-Obrovac, Ljubica; Pavlak, Marina; Mihaljević, Ivica; Mrljak, Vladimir; Štambuk, Nikola; Konjevoda, Paško; Žinić, Biserka (2005) Synthesis, spectroscopic characterization and biological activity of N-1-sulfonylcytosine derivatives. Croatica Chemica Acta, 78 (2). pp. 261-267. ISSN 0011-1643

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Abstract

Large scale preparation of N-1-sulfonylcytosine derivatives has been optimized. The best method was the condensation reaction of silylated cytosine (1) with p-toluenesulforyl 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 % yields, respectively. The NMR evidence presented shows that 2 appears as a common keto-amino tautomer in DMSO-d(6) solution while its hydrochloride 3 forms exclusively the 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 metastases of colon carcinoma (SW-620), and human Burkitt lymphoma cells (Raji). MTT-cytotoxicity screens in human tissue culture cell lines showed that both investigated compounds demonstrated antiproliferative activity in different histological types of tumors. In comparison with 5-fluorouracil, some of N-1-sulfonylcytosine derivatives showed 10 times stronger activity, with respect IC(50). The inhibitory effect of the investigated derivatives on normal human cells was lower compared to their antitumor effects. In addition to antitumor effects, hematological findings following the parenteral administration of substances were also investigated.

Item Type:	Article
Uncontrolled Keywords:	N-1-sulfonylcytosine derivatives; in vitro antiproliferative effect; antitumor activity; hematological findings; sulfonylureas; agents
Subjects:	NATURAL SCIENCES > Chemistry
Divisions:	Division of Organic Chemistry and Biochemistry NMR Center
Projects:	Project title Project leader Project code Project type Nuklearna magnetska rezonancija i proračuni bioorganskih molekula Dražen Vikić-Topić 0098059 MZOS Supramolekularna organizacija u gelovima, molekulsko prepoznavanje i kataliza Mladen Žinić 0098053 MZOS Mehanizam djelovanja novih DNA-interkalatora na stanice tumora čovjeka Ljubica Glavaš-Obrovac 0127111 MZOS Klamidofiloza ptica i sisavaca Željko Župančić 0053324 MZOS Moduliranje imunološkog odgovora bioaktivnim peptidima Biserka Pokrić 0098097 MZOS
Depositing User:	Biserka Žinić
Date Deposited:	06 Nov 2013 11:01
URI:	http://fulir.irb.hr/id/eprint/892

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