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.
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Chiang, P.K., McCann, P.P., Lane, J.R. et al. Antihuman immunodeficiency virus (HIV-1) activities of inhibitors of polyamine pathways. J Biomed Sci 3, 78–81 (1996). https://doi.org/10.1007/BF02255534
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DOI: https://doi.org/10.1007/BF02255534