In Vivo Toxicity Study of N-1-sulfonylcytosine Derivatives and Their Mechanisms of Action in Cervical Carcinoma Cell Line

Overview

Journal Invest New Drugs

Publisher Springer

Specialty Oncology

Date 2011 Mar 23

PMID 21424699

Citations 1

Authors

Jelena Kasnar-Samprec

Ivana Ratkaj

Katarina Miskovic

Marina Pavlak

Mirela Baus-Loncar

Sandra Kraljevic Pavelic

Ljubica Glavas-Obrovac

Biserka Zinic

Affiliations

Soon will be listed here.

Abstract

New N-1-sulfonylpyrimidines showed potent growth inhibitory activity against human and mouse tumour cells of different origin. 1-(p-toluenesulfonyl)cytosine (TsC) and 1-(p-toluenesulfonyl)cytosine hydrochloride (TsC × HCl) inhibited the growth of human cervical carcinoma cells (HeLa), and had no significant cytotoxic effects on normal human foreskin fibroblasts (BJ). TsC and TsC × HCl interfered with the HeLa cell cycle progression bringing about the accumulation of G1 phase cells and the induction of apoptosis. Antiproliferative effects of TsC and TsC × HCl were additionally confirmed by investigating de novo synthesis of RNA, DNA and proteins in HeLa cells. Monitoring gene expression using DNA Chip Analysis and quantitative PCR showed that TsC × HCl affects the expression of several cell-cycle regulating genes implying that cell cycle arrest and DNA damage-induced apoptosis might account for the observed cellular effects. In vivo experiments revealed low toxicity of TsC × HCl, as demonstrated by unaltered haematological and metabolic blood parameters. In conclusion, potent antitumour efficacy and low toxicity of new compounds in comparison with the common chemotherapy drug 5-FU make them promising anticancer agents. Additional pre-clinical and clinical studies are warranted to illuminate the mode of action of these newly synthesized compounds in vivo, which would lay the groundwork for their further optimization.

Citing Articles

Mass spectrometry and theoretical studies on N-C bond cleavages in the N-sulfonylamidino thymine derivatives.

Kobetic R, Kazazic S, Kovacevic B, Glasovac Z, Krstulovic L, Bajic M J Am Soc Mass Spectrom. 2015; 26(5):833-42.

PMID: 25762153 DOI: 10.1007/s13361-014-1068-8.

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