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

  • Bioorg Med Chem. 2012 Oct 1;20(19):5802-9. doi: 10.1016/j.bmc.2012.08.008.
Natalia F Zakirova  1 ,  Alexander V Shipitsyn ,  Maxim V Jasko ,  Maria M Prokofjeva ,  Valeria L Andronova ,  Georgiy A Galegov ,  Vladimir S Prassolov ,  Sergey N Kochetkov
Affiliations
  • 1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russian Federation. [email protected]
PMID: 22954898 DOI: 10.1016/j.bmc.2012.08.008
Abstract

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 50 μM. It also inhibited replication of wild-type HSV-1 (9.7 μM) as well as an acyclovir-resistant strain (25 μM). None of the synthesised compounds showed any cytotoxicity.