Design, synthesis and antiviral activity of novel quinazolinones

HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well as mechanistically different. Herein, a series of quinazolinones were designed and synthesized as novel HIV-1 inhibitors. The new synthetic route provides a practical method for the preparation of 5-hydroxy quinazolinones. Primary bioassay results indicated that most of the quinazolinones possess anti-HIV activity, especially for compound 11b with 77.5% inhibition rate at 10 μM emerged as a new active lead. Most of the synthesized compounds were also found to exhibit good anti-TMV activity, of which compound 9a showed similar in vivo anti-TMV activity to commercial plant virucide Ribavirin. This work provides a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration and optimization of previously reported antiviral agents.

A series of quinazolinone derivatives were prepared and evaluated for their anti-HIV and anti-TMV activities. The bioassay results showed that these compounds possess anti-HIV activity and in vivo anti-TMV activity.Figure optionsDownload as PowerPoint slideHighlights
► A series of quinazolinone derivatives were prepared and evaluated for anti-HIV activity.
► Most of these compounds possess anti-HIV activity and anti-TMV activity.
► Compound 11b with 77.5% HIV inhibition rate at 10 μM emerged as a new active lead.
► Compound 9a showed similar in vivo anti-TMV activity to commercial Ribavirin.
► An efficient approach to evolve novel multi-functional antiviral agents was described.