Synthesis and biological evaluation of 2-phenylquinolones targeted at Tat/TAR recognition

详细信息    查看全文

• 作者：Giuseppe Manfroni ; Barbara Gatto ; Oriana Tabarrini ; Stefano Sabatini ; Violetta Cecchetti ; Giulia Giaretta ; Cristina Parolin ; Claudia Del Vecchio ; Arianna Calistri ; Manlio Palumbo ; Arnaldo Fravolini
• 关键词：Tat/TAR complex inhibitors ; 2-Phenylquinolones ; Anti-HIV agents ; FQA
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 February 2009
• 年：2009
• 卷：19
• 期：3
• 页码：714-717
• 全文大小：161 K

文摘

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.