BIOMAT Database Logo BIOMAT Database Logo

Synthesis, cytostatic activity and ADME properties of C-5 substituted and N-acyclic pyrimidine derivatives. 2012

Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, Croatia.

The synthesis of the novel 5-alkyl pyrimidine derivatives, 5,6-dihydrofuro[2,3-d]pyrimidines and 5-alkyl N-methoxymethyl pyrimidine derivatives and evaluation of their cytostatic activities are described. The mechanism of antiproliferative effect of 5-(2-chloroethyl)-substituted pyrimidine 3 that exerted the pronounced cytostatic activity was studied in further details on colon carcinoma (HCT116) cells. The cell cycle perturbation analysis demonstrated severe DNA damage (G2/M arrest) pointing to a potential DNA alkylating ability of 3. Preliminary ADME data of 3 and its 6-methylated structural congener (6-Me-3) showed their high permeability and good metabolic stability.

UI MeSH Term Description Entries
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D010539 Permeability Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions. Permeabilities
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.
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002626 Chemistry, Pharmaceutical Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use. Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
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
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000477 Alkylating Agents Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. Alkylating Agent,Alkylator,Alkylators,Agent, Alkylating,Agents, Alkylating

Related Publications

Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Synthesis, cytostatic and anti-HIV evaluations of the new unsaturated acyclic C-5 pyrimidine nucleoside analogues.
May 2008, Bioorganic & medicinal chemistry,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Synthesis and antiviral and cytostatic evaluations of the new C-5 substituted pyrimidine and furo[2,3-d]pyrimidine 4',5'-didehydro-L-ascorbic acid derivatives.
August 2007, Journal of medicinal chemistry,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Novel C-6 fluorinated acyclic side chain pyrimidine derivatives: synthesis, (1)H and (13)C NMR conformational studies, and antiviral and cytostatic evaluations.
June 2007, Journal of medicinal chemistry,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Synthesis and properties of N-substituted saccharin derivatives.
June 2002, Die Pharmazie,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Synthesis and antiviral activity of some acyclic and C-acyclic pyrrolo[2,3-d]pyrimidine nucleoside analogues.
August 1990, Journal of medicinal chemistry,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Synthesis of densely substituted pyrimidine derivatives.
November 2009, The Journal of organic chemistry,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
The novel C-5 aryl, alkenyl, and alkynyl substituted uracil derivatives of L-ascorbic acid: synthesis, cytostatic, and antiviral activity evaluations.
January 2007, Bioorganic & medicinal chemistry,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Synthesis and biological activity of 5-phenylselenenyl-substituted pyrimidine nucleosides.
July 1986, Journal of medicinal chemistry,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Design, synthesis and antitumor activity evaluation of trifluoromethyl-substituted pyrimidine derivatives.
November 2021, Bioorganic & medicinal chemistry letters,
Tatjana Gazivoda Kraljević, and Mateja Klika, and Marijeta Kralj, and Irena Martin-Kleiner, and Stella Jurmanović, and Astrid Milić, and Jasna Padovan, and Silvana Raić-Malić
Antiviral and cytostatic evaluation of the novel 6-acyclic chain substituted thymine derivatives.
January 2005, Antiviral chemistry & chemotherapy,
Copied contents to your clipboard!