title: 3-Phenylcoumarins as inhibitors of HIV-1 replication.
abstract: We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC₅₀ values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Salamanca, CIETUS-IBSAL, 37007 Salamanca, Spain.
authors.forename: Dionisio
authors.initials: D
authors.lastname: Olmedo
authors.forename: Rocío
authors.initials: R
authors.lastname: Sancho
authors.forename: Luis M
authors.initials: LM
authors.lastname: Bedoya
authors.forename: José L
authors.initials: JL
authors.lastname: López-Pérez
authors.forename: Esther
authors.initials: E
authors.lastname: Del Olmo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
authors.forename: José
authors.initials: J
authors.lastname: Alcamí
authors.forename: Mahabir P
authors.initials: MP
authors.lastname: Gupta
authors.forename: Arturo
authors.initials: A
authors.lastname: San Feliciano
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D017930:Genes, Reporter; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors
chemical_list: D019380:Anti-HIV Agents; D003374:Coumarins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; C094411:4-phenylcoumarin; D008156:Luciferases