Abstract
A series of acyclic selenopurine nucleosides 3a-f and 4a-g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a) exhibited the most potent anti-herpes simplex virus (HSV)-1 (EC50 = 1.47 µM) and HSV-2 (EC50 = 6.34 µM) activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e-g exhibited significant anti-human cytomegalovirus (HCMV) activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d).
Keywords:
acyclic selenopurine nucleoside; anti-herpetic; antiviral; prodrug.
MeSH terms
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2-Aminopurine / analogs & derivatives
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2-Aminopurine / chemical synthesis
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2-Aminopurine / pharmacology
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Acyclovir / analogs & derivatives
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Acyclovir / chemical synthesis
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Acyclovir / pharmacology
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / pharmacology
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Cytomegalovirus / drug effects
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Guanine / analogs & derivatives
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Guanine / chemical synthesis
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Guanine / pharmacology
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Herpesvirus 1, Human / drug effects
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Herpesvirus 2, Human / drug effects
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Humans
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Nucleosides / chemical synthesis*
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Nucleosides / pharmacology
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Organoselenium Compounds / chemical synthesis*
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Organoselenium Compounds / pharmacology
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Prodrugs / chemical synthesis
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Prodrugs / pharmacology
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Purines / chemical synthesis*
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Purines / pharmacology
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Simplexvirus / drug effects
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Structure-Activity Relationship
Substances
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Antiviral Agents
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Nucleosides
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Organoselenium Compounds
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Prodrugs
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Purines
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2-Aminopurine
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2,6-diaminopurine
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Guanine
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Acyclovir