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Synthesis, cytotoxicity and antiviral activity of N,N'-bis-5-nitropyrimidyl derivatives of dispirotripiperazine.
- Source :
-
Antiviral research [Antiviral Res] 2002 Jul; Vol. 55 (1), pp. 117-27. - Publication Year :
- 2002
-
Abstract
- 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.
- Subjects :
- Animals
Antiviral Agents chemical synthesis
Antiviral Agents toxicity
Cell Line
Chlorocebus aethiops
Cytopathogenic Effect, Viral drug effects
Dogs
Dose-Response Relationship, Drug
HeLa Cells
Herpesvirus 1, Human physiology
Humans
Piperazines chemical synthesis
Piperazines toxicity
Spiro Compounds chemical synthesis
Spiro Compounds toxicity
Structure-Activity Relationship
Virus Replication drug effects
Antiviral Agents pharmacology
Herpesvirus 1, Human drug effects
Piperazines pharmacology
Spiro Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0166-3542
- Volume :
- 55
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 12076756
- Full Text :
- https://doi.org/10.1016/s0166-3542(02)00014-1