title: Synthesis and biological evaluation of 2-phenylquinolones targeted at Tat/TAR recognition.
abstract: Tat (transactivator of transcription) is a small HIV protein rich in arginines that interacts with a viral RNA structure called TAR (trans-activation responsive region). Tat-TAR interaction is essential for viral gene expression, replication and pathogenesis. Small molecules able to interfere with TAR and to compete for Tat binding possess antiviral activity due to inhibition of viral transcription and expression, thus impairing formation of infectious virions. We report here, the synthesis and biological evaluation of a new series of quinolone derivatives, namely 2-phenylquinolones, designed with the aim of interfering with the protein/RNA complex. These new derivatives are able to efficiently interfere with Tat/TAR complex in vitro depending on precise structural requirements as demonstrated by fluorescence quenching assay analysis.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Manfroni
authors.forename: Barbara
authors.initials: B
authors.lastname: Gatto
authors.forename: Oriana
authors.initials: O
authors.lastname: Tabarrini
authors.forename: Stefano
authors.initials: S
authors.lastname: Sabatini
authors.forename: Violetta
authors.initials: V
authors.lastname: Cecchetti
authors.forename: Giulia
authors.initials: G
authors.lastname: Giaretta
authors.forename: Cristina
authors.initials: C
authors.lastname: Parolin
authors.forename: Claudia
authors.initials: C
authors.lastname: Del Vecchio
authors.forename: Arianna
authors.initials: A
authors.lastname: Calistri
authors.forename: Manlio
authors.initials: M
authors.lastname: Palumbo
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Fravolini
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008956:Models, Chemical; D010446:Peptide Fragments / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry; D012367:RNA, Viral / Q000378:metabolism; D013050:Spectrometry, Fluorescence / Q000379:methods; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D010446:Peptide Fragments; D015363:Quinolones; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus