title: In vitro anti-HIV potency of stampidine alone and in combination with standard anti-HIV drugs.
abstract: The purpose of the present study was compare the in vitro anti-HIV potency stampidine (CAS 217178-62-6), a novel aryl phosphate derivative of stavudine (CAS 3056-17-5), and drug combinations containing stampidine to the anti-HIV tency of the standard drugs zidovudine (CAS 30516-87-1), stavudine, lamivudine (CAS 134678-17-4), nelfinavir (CAS 159989-65-8), and nevirapine (CAS 129618-40-2) as well as their combinations. Stampidine inhibited the laboratory HIV-1 strain HTLV(IIIB) (B-envelope subtype) as well as the primary clinical HIV-1 isolates BR/92/025 (C-envelope subtype) and BR/93/20 (F-envelope sub-type) with subnanomolar IC50 values. Stampidine was as effective as zidovudine against HTLV(IIIB) and BR/92/025 and 3-logs more effective than zidovudine against BR/93/20. Stampidine was more effective than stavudine, lamivudine, nelfinavir, and nevirapine against all three HIV-1 isolates. The combination of stampidine with zidovudine + lamivudine was more effective than the combination of nelfinavir or nevirapine with zidovudine lamivudine against all three HIV-1 isolates. The combination of stampidine with nelfinavir was more effective than zidovudine + lamivudine as well as the combination of zidovudine + lamivudine with nelfinavir. The combination of stampidine with lamivudine + nelfinavir was more effective than the combination of zidovudine with lamivudine + nelfinavir. The combination of stampidine with lamivudine + nevirapine was more effective than the combination of stavudine with lamivudine + nevirapine. These findings demonstrate that (a) stampidine, as well as its combinations with the standard anti-HIV drugs zidovudine, lamivudine, nelfinavir or nevirapine, are potent inhibitors of HIV-1 replication in human peripheral blood mononuclear cells, and (b) replacement of either zidcovudine, zidovudine+lamivudine or stavudine in 3-drug cocktails with stampidine resulted in greater anti-HIV potency in vitro.
authors.affiliation: Drug Discovery Program, Department of Virology, Parker Hughes Institute, St Paul, MN 55113, (USA). fatih_uckun@ih.org
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
authors.forename: Sanjive
authors.initials: S
authors.lastname: Qazi
authors.forename: T K
authors.initials: TK
authors.lastname: Venkatachalam
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D054306:Dideoxynucleotides; D004338:Drug Combinations; D004347:Drug Interactions; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D016018:Least-Squares Analysis; D008962:Models, Theoretical; D019888:Nelfinavir / Q000494:pharmacology; D019829:Nevirapine / Q000494:pharmacology; D010641:Phenotype; D018119:Stavudine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D054306:Dideoxynucleotides; D004338:Drug Combinations; C472384:stampidine; D019259:Lamivudine; D013938:Thymidine Monophosphate; D015215:Zidovudine; D019829:Nevirapine; D018119:Stavudine; D019888:Nelfinavir