Synthesis and biological evaluation of 2-phenylquinolones targeted at Tat/TAR recognition.
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.
Manfroni
Giuseppe
G
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Gatto
Barbara
B
Tabarrini
Oriana
O
Sabatini
Stefano
S
Cecchetti
Violetta
V
Giaretta
Giulia
G
Parolin
Cristina
C
Del Vecchio
Claudia
C
Calistri
Arianna
A
Palumbo
Manlio
M
Fravolini
Arnaldo
A
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*
D019380:Anti-HIV Agents; D010446:Peptide Fragments; D015363:Quinolones; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus