Antihuman Immunodeficiency Virus (HIV-1) Activities of Inhibitors of Polyamine Pathways.
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 alpha-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 IC(50) values of about 1-2 &mgr;M. 5'--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 IC(50) values of 1-2 &mgr;M. The least potent was 1-aminoxyethylamine which is another inhibitor of AdoMet decarboxylase. MAP showed the best therapeutic index of 500-1,000. Copyright 1996 S. Karger AG, Basel
Chiang
P.K.
PK
Division of Retrovirology, Walter Reed Army Institute of Research, Washington, D.C., USA.
McCann
P.P.
PP
Lane
J.R.
JR
Pankaskie
M.C.
MC
Burke
D.S.
DS
Mayers
D.L.
DL