Inhibition of HIV-1 IIIb replication in AA-2 and MT-2 cells in culture by two ligands of poly (ADP-ribose) polymerase: 6-amino-1,2-benzopyrone and 5-iodo-6-amino-1,2-benzopyrone.
The effects of two adenosine diphosphoribose transferase (ADPRT) enzyme inhibitory ligands, 6-amino-1,2-benzopyrone and its 5-iodo-derivative, were determined in AA-2 and MT-2 cell cultures on the replication of HIV-1 IIIb, assayed by an immunochemical test for the HIV protein p24, and syncytium formation, characteristic of HIV-infected cells. Intracellular concentrations of both drugs were sufficient to inhibit poly(ADP-ribose) polymerase activity within the intact cell. Both drugs inhibited HIV replication parallel to their inhibitory potency on ADPRT, but distinct differences were ascertained between the two cell lines. In AA-2 cells both p24 and syncytium formation were depressed simultaneously, whereas in MT-2 cells only syncytium formation was inhibited by the drugs, and the p24 production, which remained unchanged during viral growth, was unaffected. Both drugs only moderately depressed the growth rate of the AA-2 and MT-2 cells and there was no detectable cellular toxicity. Results suggest the feasibility of the development of a new line of ADPRT ligand anti-HIV drugs that fundamentally differ in their mode of action from currently used chemotherapeutics.
Cole
G A
GA
Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore 21201.
Bauer
G
G
Kirsten
E
E
Mendeleyev
J
J
Bauer
P I
PI
Buki
K G
KG
Hakam
A
A
Kun
E
E
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003374:Coumarins / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D003374:Coumarins; D008024:Ligands; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C071383:5-iodo-6-amino-1,2-benzopyrone; C067496:6-amino-1,2-benzopyrone