BIOMAT Database Logo BIOMAT Database Logo

The unsaturated acyclic nucleoside analogues bearing a sterically constrained (Z)-4'-benzamido-2'-butenyl moiety: Synthesis, X-ray crystal structure study, cytostatic and antiviral activity evaluations. 2010

Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, 10000 Zagreb, Croatia.

A series of the novel acyclic unsaturated pyrimidine (1-12) and adenine (13) nucleoside analogues bearing conformationally restricted (Z)-2'-butenyl moiety were synthesized and evaluated for their antiviral and cytostatic activity potency against malignant tumor cell lines and normal human fibroblast (WI38). The N-1 and/or N-3 acyclic side chain substitution in pyrimidine ring in N-3 substituted 5-trifluoromethyluracil derivative (11), N-1, N-3 disubstituted 5-fluorouracil derivative (12) and adenine derivative (13) was deduced from their (1)H and (13)C NMR spectra and confirmed by single crystal X-ray structure analysis. The X-ray crystal structure analysis 11-13 revealed also supramolecular self-assemblies, in which infinite chains or dimers built two- and three-dimensional networks. The results of the in vitro cytostatic activity evaluations of 1-13 indicate that the majority of the compounds tested exhibited a non-specific and moderate antiproliferative effect at the highest concentration (100 microM). Of all evaluated compounds on the cell lines tested only the N-1 4''-fluoro-substituted-benzamide uracil derivative (7) showed rather marked and selective inhibitory activity against the growth of MCF-7 cells at a concentration of 2.7 microM and no cytotoxic effect on normal fibroblasts WI38. This compound can be therefore considered as a potential antitumor lead compound for further synthetic structure modification.

UI MeSH Term Description Entries
D007536 Isomerism The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Isomerisms
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
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.
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
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000225 Adenine A purine base and a fundamental unit of ADENINE NUCLEOTIDES. Vitamin B 4,4, Vitamin B,B 4, Vitamin
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

Related Publications

Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Synthesis, X-ray crystal structural study, antiviral and cytostatic evaluations of the novel unsaturated acyclic and epoxide nucleoside analogues.
December 2006, Bioorganic & medicinal chemistry,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Synthesis, cytostatic and anti-HIV evaluations of the new unsaturated acyclic C-5 pyrimidine nucleoside analogues.
May 2008, Bioorganic & medicinal chemistry,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
The novel L- and D-amino acid derivatives of hydroxyurea and hydantoins: synthesis, X-ray crystal structure study, and cytostatic and antiviral activity evaluations.
January 2005, Journal of medicinal chemistry,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Unsaturated and carbocyclic nucleoside analogues: synthesis, antitumor, and antiviral activity.
January 1991, Journal of medicinal chemistry,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Short synthesis and antiviral activity of acyclic phosphonic acid nucleoside analogues.
February 2009, Nucleosides, nucleotides & nucleic acids,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Synthesis and antiviral activity of some acyclic and C-acyclic pyrrolo[2,3-d]pyrimidine nucleoside analogues.
August 1990, Journal of medicinal chemistry,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
The synthesis and antiviral activity of some 4'-thio-2'-deoxy nucleoside analogues.
September 1991, Journal of medicinal chemistry,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Synthesis and antiviral activity of novel acyclic nucleoside analogues of 5-(1-azido-2-haloethyl)uracils.
November 2001, Journal of medicinal chemistry,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Synthesis, X-ray crystal structure study, and cytostatic and antiviral evaluation of the novel cycloalkyl-N-aryl-hydroxamic acids.
February 2005, Journal of medicinal chemistry,
Kresimir Benci, and Karlo Wittine, and Malajka Radan, and Mario Cetina, and Mirela Sedić, and Sandra Kraljević Pavelić, and Kresimir Pavelić, and Erik De Clercq, and Mladen Mintas
Geiparvarin analogues. 4. Synthesis and cytostatic activity of geiparvarin analogues bearing a carbamate moiety or a furocoumarin fragment on the alkenyl side chain.
July 1994, Journal of medicinal chemistry,
Copied contents to your clipboard!