Journal of Biomedical Science

, Volume 3, Issue 2, pp 78–81 | Cite as

Antihuman immunodeficiency virus (HIV-1) activities of inhibitors of polyamine pathways

  • Peter K. Chiang
  • Peter P. McCann
  • James R. Lane
  • Marvin C. Pankaskie
  • Donald S. Burke
  • Douglas L. Mayers
Original Paper

Abstract

Four inhibitors of polyamine biosynthetic pathways were tested for their effect on HIV-1 replication in phytohemagglutinin-stimulated human peripheral blood mononuclear cells. Methyl acetylenic putrescine (MAP) and α-monofluoromethyldehydroornithine methyl ester, irreversible inhibitors of ornithine decarboxylase, inhibited the production of p24 antigen in phytohemagglutinin-stimulated peripheral blood mononuclear cells by clinical HIV-1 strains isolated from HIV-infected patients with IC50 values of about 1–2 µM. 5′-{(Z)-4-amino-2-butenyl]methylamino}-5′-deoxyadenosine (MDL 73811), an enzyme-activated irreversible inhibitor of S-adenosyl-L-methionine (AdoMet) decarboxylase, also inhibited the production of p24 antigen by HIV-1 strains in peripheral blood mononuclear cells with IC50 values of 1–2 µM. The least potent was 1-aminoxyethylamine which is another inhibitor of AdoMet decarboxylase. MAP showed the best therapeutic index of 500–1,000.

Key Words

HIV-1 Polyamines Inhibitors p24 S-adenosylmethionine 

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Copyright information

© National Science Council 1996

Authors and Affiliations

  • Peter K. Chiang
    • 4
  • Peter P. McCann
    • 1
  • James R. Lane
    • 2
  • Marvin C. Pankaskie
    • 3
  • Donald S. Burke
    • 4
  • Douglas L. Mayers
    • 4
  1. 1.British Biotech Inc.Annapolis
  2. 2.SRA TechnologiesRockville
  3. 3.University of Nebraska Medical CenterOmahaUSA
  4. 4.Division of RetrovirologyWalter Reed Army Institute of ResearchWashington, DCUSA

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