title: Quinoline-based compounds as modulators of HIV transcription through NF-kappaB and Sp1 inhibition.
abstract: 18 quinoline-based compounds were tested for antiviral properties against human immunodeficiency syndrome (HIV). The compounds tested here contain quinoline or tetrahydroquinoline rings and can be divided into two main groups: group 1 includes 4-(2-oxopyrrolidinyl-1)-1,2,3,4-tetrahydroquinolines with 2-(3-nitrophenyl) substituent (N-series) or 2-(3-aminophenyl) moiety (H-series), and group 2 includes 2-(3-nitrophenyl)- or 2-(3-aminophenyl)-substituted quinolines (S-series). Two different antiviral assays were performed in order to test the anti-HIV activity of compounds: 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and recombinant virus assay (RVA). Results showed that the most active compounds were 2-aryl quinolines, particularly those containing methoxy substituents or no substituents in the quinoline skeleton. HIV transcription inhibition appears to be their target in both resting and phorbol myristate acetate (PMA) activated primary lymphocytes, and nuclear factor-kappaB (NF-kappaB) and specificity protein-1 (SP1) seems to be the most important transcription factors involved in their action.
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Crt. Majadahonda a Pozuelo, 28220 Majadahonda, Madrid, Spain.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Bedoya
authors.forename: María José
authors.initials: MJ
authors.lastname: Abad
authors.forename: Esther
authors.initials: E
authors.lastname: Calonge
authors.forename: Luis Astudillo
authors.initials: LA
authors.lastname: Saavedra
authors.forename: Margarita
authors.initials: M
authors.lastname: Gutierrez C
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Kouznetsov
authors.forename: José
authors.initials: J
authors.lastname: Alcami
authors.forename: Paulina
authors.initials: P
authors.lastname: Bermejo
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D000998:Antiviral Agents; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D011804:Quinolines; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1