title: Significant anti-HIV activity of new modified polyanionic polymers in vitro.
abstract: The anti-HIV activities of two new polyanionic polymers (AM 242 and AM 612) were investigated in cell culture-based and biochemical antiviral assays. These compounds inhibited the reverse transcriptases from HIV-1 and HIV-2, using enzyme purified from virions and either a ribosomal RNA or gapped duplex DNA as the template. With the ribosomal RNA template, AM 242 and AM 612 had ID50 values of 1.1 and 0.10 micrograms/ml against the HIV-1 reverse transcriptase. In vitro cell based assays determined that both compounds significantly inhibited both the cytopathic effects associated with HIV-1 infection and the replication of virus in infected cells. AM 242 had an IC50 of approximately 1.0 micrograms/ml, while that of AM 612 was 0.19 micrograms/ml. These two active polyanionic polymers were effective in inhibiting the growth of a panel of HIV-1 isolates and were also active against HIV-2. Although the compounds were toxic at high concentration, they had antiviral activity over a wide range of nontoxic concentrations, yielding a high selectivity index. AM 612 was 100% protective for CEM cells from 320 ng/ml to 1 microgram/ml. Both compounds caused a significant increase in cellular proliferation as determined by the concentration-dependent increase in incorporation of radioactive precursors into cellular macromolecules.
authors.affiliation: Southern Research Institute, Birmingham, Alabama.
authors.forename: R W
authors.initials: RW
authors.lastname: Buckheit
authors.forename: E L
authors.initials: EL
authors.lastname: White
authors.forename: W M
authors.initials: WM
authors.lastname: Shannon
authors.forename: A
authors.initials: A
authors.lastname: Guerrero
authors.forename: J P
authors.initials: JP
authors.lastname: Pivel
authors.forename: L
authors.initials: L
authors.lastname: Carrasco
authors.forename: J A
authors.initials: JA
authors.lastname: Leal
authors.forename: M A
authors.initials: MA
authors.lastname: Chirigos
mesh_terms: D000838:Anions / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D011108:Polymers / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000838:Anions; D000998:Antiviral Agents; D011108:Polymers; D015215:Zidovudine; D004247:DNA