Metabolic effects of novel N-1-sulfonylpyrimidine derivatives on human colon carcinoma cells. 2005

Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
Department of Nuclear Medicine, Radiation Protection, and Pathophysiology, Clinical Hospital Osijek, Huttlerova 4, 31000 Osijek, Croatia. obrovacg2@hotmail.com

Novel N-1-sulfonylpyrimidine derivatives have a strong antiproliferative activity and an ability to induce apoptosis in treated tumor cells. The purpose of this study was to elucidate the effects of two N-1-sulfonylpyrimidine nucleobases on catalytic activity of tumor cells' enzymes involved in DNA and RNA synthesis, and in de novo and salvage pyrimidine and purine syntheses. Investigations were performed in vitro on colon carcinoma cells (Caco2). The biosynthetic activity of the tumor cells' enzymes was determined using sensitive radio-assays. Enzyme activity in treated cells was calculated relative to untreated control cells. Both of the investigated compounds, 1-(p-toluenesulfonyl) cytosine (TsC) and 5-bromo-1-(methanesulfonyl) uracil (BMsU) inhibited activities of specific enzymes involved in nucleic acid synthesis. BMsU strongly inhibited activities of DNA polymerase alpha (53%), thymidine kinase (68%), thymidilate synthase (43%), and ribonucleotide reductase (46%). De novo biosynthesis of pyrimidine and purine was reduced by 20%. TsC was able to inhibit RNA polymerase (37%), orotate phosphoribosyltransferase (39%), uridine kinase (44%), ribonucleotid reductase (47%), and de novo purine synthesis (61%). Antitumor activity of 1-(p-toluenesulfonyl) cytosine (TsC) and 5-bromo-1-(methanesulfonyl) uracil (BMsU) is closely associated with their inhibitory activity on enzymes that play an important role in the metabolism of tumor cells.

UI MeSH Term Description Entries
D008698 Mesylates Organic salts or esters of methanesulfonic acid. Mesilate,Methanesulfonates,Mesilates,Mesylate,Methylenesulfonates
D009962 Orotate Phosphoribosyltransferase The enzyme catalyzing the formation of orotidine-5'-phosphoric acid (orotidylic acid) from orotic acid and 5-phosphoribosyl-1-pyrophosphate in the course of pyrimidine nucleotide biosynthesis. EC 2.4.2.10. Orotidine-5'-Phosphate Pyrophosphorylase,Orotidylic Acid Phosphorylase,OMPase,Orotidine-5'-Monophosphate Phosphohydrolase,Orotidine 5' Monophosphate Phosphohydrolase,Orotidine 5' Phosphate Pyrophosphorylase,Phosphohydrolase, Orotidine-5'-Monophosphate,Phosphoribosyltransferase, Orotate,Phosphorylase, Orotidylic Acid,Pyrophosphorylase, Orotidine-5'-Phosphate
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004256 DNA Polymerase I A DNA-dependent DNA polymerase characterized in prokaryotes and may be present in higher organisms. It has both 3'-5' and 5'-3' exonuclease activity, but cannot use native double-stranded DNA as template-primer. It is not inhibited by sulfhydryl reagents and is active in both DNA synthesis and repair. DNA Polymerase alpha,DNA-Dependent DNA Polymerase I,Klenow Fragment,DNA Pol I,DNA Dependent DNA Polymerase I,Polymerase alpha, DNA
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001221 Aspartate Carbamoyltransferase An enzyme that catalyzes the conversion of carbamoyl phosphate and L-aspartate to yield orthophosphate and N-carbamoyl-L-aspartate. (From Enzyme Nomenclature, 1992) EC 2.1.3.2. Aspartate Transcarbamylase,Co(II)-Aspartate Transcarbamoylase,Ni(II)-Aspartate Transcarbamoylase,Carbamoyltransferase, Aspartate,Transcarbamylase, Aspartate

Related Publications

Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
March 2009, Bioorganic & medicinal chemistry,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
October 1984, Journal of the National Cancer Institute,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
January 2015, Toxicology mechanisms and methods,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
July 2021, Zeitschrift fur Naturforschung. C, Journal of biosciences,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
January 2014, BioMed research international,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
October 1990, Biochemical pharmacology,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
November 2019, Gene,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
June 1999, Carcinogenesis,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
April 1979, Cancer research,
Ljubica Glavas-Obrovac, and Ivan Karner, and Mario Stefanić, and Jelena Kasnar-Samprec, and Biserka Zinić
February 2005, Biological & pharmaceutical bulletin,
Copied contents to your clipboard!