title: Antiviral, cytotoxic and apoptotic activities of picolinic acid on human immunodeficiency virus-1 and human herpes simplex virus-2 infected cells.
abstract: The antiviral, cytotoxic and apoptotic effects of picolinic acid against human immunodeficiency virus-1 (HIV-1) and human herpes simplex virus-2 (HSV-2) infected cells were evaluated in cultured cells using in vitro assays. Picolinic acid was tested at several concentrations (from 0.15 to 3 mM) against one input dilution of the viruses to determine if the agent had any antiviral activity against HIV-1 or HSV-2. The results showed that picolinic acid at 1.5 mM (185 ug/mL) and 3 mM (369 ug/mL) was active against HIV-1 and HSV-2-infected cells, causing cytotoxicity which resulted in apoptosis and lack of viral replication. In parallel control experiments with non-infected cells, picolinic acid also caused cytotoxicity and apoptosis, which was more prominent at 3 mM than at 1.5 mM. Thus, infected cells appear to be slightly more sensitive to the cytotoxic and apoptotic effects of picolinic acid. The overlapping of the antiviral profile with the cytotoxic profile of picolinic acid indicates that, in vitro, the most likely sequence of events is that picolinic acid initially causes cytotoxicity which in turn results in apoptosis of cells infected with HIV-1 or HSV-2 and thus reduces the amount of viral replication.
authors.affiliation: Laboratory of Molecular Oncology, DVA Medical Center, St. Louis, MO 63106, USA. fernandezpol@earthlink.net
authors.forename: J A
authors.initials: JA
authors.lastname: Fernandez-Pol
authors.forename: D J
authors.initials: DJ
authors.lastname: Klos
authors.forename: P D
authors.initials: PD
authors.lastname: Hamilton
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000633:toxicity; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010848:Picolinic Acids / Q000494:pharmacology* / Q000633:toxicity; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D010848:Picolinic Acids; C030614:picolinic acid