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Synthesis, Spectroscopic Characterization and Biological Activity of N-1-Sulfonylcytosine Derivatives

Croatian International Relations Review

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Title Synthesis, Spectroscopic Characterization and Biological Activity of N-1-Sulfonylcytosine Derivatives
Sinteza, spektroskopska karakterizacija i biološka aktivnost N-1-sulfonilcitozinskih derivata
 
Creator Kašnar-Šamprec, Jelena
Glavaš-Obrovac, Ljubica
Pavlak, Marina
Mihaljević, Ivica
Mrljak, Vladimir
Štambuk, Nikola
Konjevoda, Paško
Žinić, Biserka
 
Subject N-1-sulfonylcytosine derivatives: in vitro antiproliferative effect; antitumor activity; hematological findings
 
Description 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 % yields, 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 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 IC50. 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.
Optimizirana je priprava većih količina N-1-sulfonilcitozinskih derivata, kondenzacijom sililiranoga citozina i p-toluensulfonil klorida u acetonitrilu. Ovisno o načinu izolacije dobiveni su 1-(p-toluensulfonil)citozin 2 (80 %) i 1-(p-toluensulfonil)citozin hidroklorid 3 (75 %). NMR eksperimenti pokazuju isključivo nastajanje keto-imino tautomera 3 u DMSO-d6 otopini, dok se 2 pojavljuje u uobičajenome keto-amino obliku. Ispitivani su potencijalni citotoksični učinci N-1-sulfonilcitozinskih derivata 2 i 3 na fibroblastima čovjeka (WI38), stanicama adenokarcinoma gušterače (MIAPaCa2), slabo diferenciranim metastazama adenokarcinoma debelog crijeva (SW-620) i stanicama Burkitt-ovog limfoma (Raji). Rezultati dobiveni MTT-testom pokazuju da ispitivani spojevi djeluju antiproliferativno na različite histološke tipove tumora. U usporedbi s 5-fluorouracilom, N-1-sulfonilcitozinski derivati pokazuju 10 puta jaču inhibiciju rasta izloženih tumorskih stanica. Inhibicijski učinci ispitivanih spojeva na normalne stanice značajno su slabiji u odnosu na protutumorske učinke. Osim antitumorskoga učinka, ispitivani su i hematološki parametri poslije parenteralne primjene ispitivanih tvari.
 
Publisher Croatian Chemical Society
 
Date 2005
 
Type text
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
 
Format application/pdf
 
Identifier https://hrcak.srce.hr/20
https://hrcak.srce.hr/file/20
 
Source Croatica Chemica Acta
ISSN 0011-1643 (Print)
ISSN 1334-417X (Online)
Volume 78
Issue 2
 
Language eng
 
Rights info:eu-repo/semantics/openAccess
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