Antihuman immunodeficiency virus (HIV-1) activities of inhibitors of polyamine pathways |
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Authors: | Peter K Chiang Peter P McCann James R Lane Marvin C Pankaskie Donald S Burke Douglas L Mayers |
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Institution: | (1) British Biotech Inc., Annapolis, Md.;(2) SRA Technologies, Rockville, Md.;(3) University of Nebraska Medical Center, Omaha, Nebr., USA;(4) Division of Retrovirology, Walter Reed Army Institute of Research, 20307-5100 Washington, DC, USA |
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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 -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. |
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Keywords: | HIV-1 Polyamines Inhibitors p24 S-adenosylmethionine |
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