Inhibition of the Moloney murine leukemia virus cycle at a post reverse transcriptional step by the netropsin-intercalating hybrid molecule netropsin-oxazolopyridocarbazole.
In a search for new antiretroviral agents acting at the nucleic acid level, two hybrid molecules composed of a bispyrrolecarboxamide chain related to netropsin, linked to the intercalating chromophore oxazolopyridocarbazole, were tested on the cycle of a defective Moloney murine leukemia virus (M.MuLV) derived from the SVX shuttle and expressing resistance to the G418 antibiotic. The drug netropsin-oxazolopyridocarbazole (Net-OPC), which displays a binding preference to duplex DNA containing A + T bases, inhibits the retroviral replicative cycle (IC50 = 4.8 microM). In contrast, the related molecule (bis)pyrollecarboxamide-oxazolopyridocarbazole (Bpc-OPC) devoid of sequence preference as well as the elemental components of Net-OPC, namely OPC, pentyl-OPC and netropsin, displays no significant action on the viral cycle. The estimation of cytosolic viral DNA in infected cells using quantitative polymerase chain reaction suggests that Net-OPC impairs a post retrotranscriptional step of the viral cycle.
Laboratoire de Biochimie-Enzymologie, INSERM U140, CNRS URA 147, Institut Gustave Roussy, Villejuif, France.
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Auclair
D016475:3T3 Cells / Q000187:drug effects / Q000382:microbiology; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002227:Carbazoles / Q000494:pharmacology*; D004274:DNA, Recombinant / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D004351:Drug Resistance; D007364:Intercalating Agents / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D009429:Netropsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
D002227:Carbazoles; D004274:DNA, Recombinant; D004279:DNA, Viral; D007364:Intercalating Agents; C067255:netropsin-oxazolopyridocarbazole; D015215:Zidovudine; D009429:Netropsin