Synthesis, cytotoxicity and antiviral activity of N,N′-bis-5-nitropyrimidyl derivatives of dispirotripiperazine
| Autor: | H.-M Dahse, Vadim Makarov, Olga B. Riabova, Michaela Schmidtke, Axel Stelzner |
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| Rok vydání: | 2002 |
| Předmět: |
Pyrimidine
Stereochemistry Chemical structure Herpesvirus 1 Human Virus Replication Antiviral Agents Chemical synthesis Piperazines Cell Line Structure-Activity Relationship chemistry.chemical_compound Dogs Cytopathogenic Effect Viral Virology Chlorocebus aethiops Animals Humans Structure–activity relationship Spiro Compounds Cytotoxicity Pharmacology Dose-Response Relationship Drug Chemistry Biological activity Nitro HeLa Cells Methyl group |
| Zdroj: | Antiviral Research. 55:117-127 |
| ISSN: | 0166-3542 |
| DOI: | 10.1016/s0166-3542(02)00014-1 |
| Popis: | During the search for new antivirals, various N,N'-bis-5-pyrimidyl derivatives of 3,12-diaza-6,9-diazonia(5,2,5,2)dispirohexadecane dichloride (dispirotripiperazine) were synthesized. To reveal relationships between chemical structure and antiviral activity, the compounds were characterized by fast atom bombardment mass, nuclear magnetic resonance, infra red spectroscopy, and elemental analysis and examined for cytotoxicity, inhibition of cell growth and antiviral activity under in vitro conditions. The results of this study demonstrate an excellent compatibility of the test compounds for confluent as well as proliferating cells and a potent structure-dependent inhibition of herpes simplex virus type 1 replication when added during viral adsorption. Functional group analysis revealed that both the dispirotripiperazine as well as the pyrimidine ring with a nitro group in the 5 position are necessary for activity. A reduction of electron density in the terminal pyrimidine rings enhanced the antiviral activity whereas electron donor substitutions reduced it. Introduction of a methyl group in position 2 of the pyrimidine had no influence on cytotoxicity or antiviral activity. |
| Databáze: | OpenAIRE |
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