Phosphoramidate derivatives of acyclovir: Synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro

The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replicat...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 2012-10, Vol.20 (19), p.5802-5809
Hauptverfasser:	Zakirova, Natalia F., Shipitsyn, Alexander V., Jasko, Maxim V., Prokofjeva, Maria M., Andronova, Valeria L., Galegov, Georgiy A., Prassolov, Vladimir S., Kochetkov, Sergey N.
Format:	Artikel
Sprache:	eng
Schlagworte:	acyclovir Acyclovir (ACV) Acyclovir - analogs & derivatives Acyclovir - chemical synthesis Acyclovir - pharmacology Animals Antiviral activity Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology antiviral properties Cercopithecus aethiops chemistry Cytotoxicity guanine HEK293 Cells Herpes Simplex - drug therapy Herpes Simplex Virus (HSV) Herpes simplex virus 1 Herpesvirus 1, Human - drug effects HIV Infections - drug therapy HIV-1 - drug effects Human Immunodeficiency Virus (HIV) Human immunodeficiency virus 1 Humans Phosphoramidates Replication Vero Cells virus replication Virus Replication - drug effects
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Zusammenfassung:	The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50μM. It also inhibited replication of wild-type HSV-1 (9.7μM) as well as an acyclovir-resistant strain (25μM). None of the synthesised compounds showed any cytotoxicity.
ISSN:	0968-0896 1464-3391
DOI:	10.1016/j.bmc.2012.08.008