Activity of the (R)-enantiomers of 9-(2-phosphonylmethoxypropyl)-adenine and 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine against human immunodeficiency virus in different human cell systems

Biochem Biophys Res Commun. 1996 Feb 15;219(2):337-41. doi: 10.1006/bbrc.1996.0234.

Abstract

The (S)- and (R)-enantiomers of 9-(2-phosphonylmethoxypropyl) derivatives of adenine (PMPA) and 2,6-diaminopurine (PMPDAP) were evaluated for their inhibitory effect on HIV replication in several human cell systems, including natural peripheral blood lymphocytes (PBL) and freshly isolated monocyte/macrophages (M/M). The (R)-enantiomers of PMPDAP and PMPA were approximately 10-to-100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PMPA was comparable to that of the prototype acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and selective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 microM for HIV-1/Ba-L in M/M to 1-2.8 microM for HIV-1/IIIB and HIV-1/HE in C8166, CEM, Molt/4, MT-4 and PBL cells. Both (R)-PMPA and (R)-PMPDAP were not toxic to the host cells at 300 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • HIV-1 / drug effects*
  • Humans
  • Organophosphonates*
  • Organophosphorus Compounds / pharmacology*
  • Soman / analogs & derivatives*
  • Soman / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine
  • Antiviral Agents
  • Organophosphonates
  • Organophosphorus Compounds
  • pinacolyl methylphosphonic acid
  • adefovir
  • Soman
  • Adenine