Synthesis and Biological Evaluation of Quinolone Acid Derivatives Having Polyhydroxylated Aromatics as HIV-1 Integrase Inhibitions

Abstract

A small chemical library of quinolone acid derivatives were synthesized as potential HIV-1 integrase inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase. Their structures were characterized by NMR, MS and HRMS. The result indicates that quinolone acid derivatives having 3,4,5-trihydroxylated aromatic substituent on the N-1 position of quinolone ring exhibit good inhibition with IC50 of 2.6 μM.

Recent advances in the synthesis of pharmaceutically active 4-quinolone and its analogues: a review

“…It was revealed that the presence of an appropriate substituent at the N-1 position is crucial to enhance the structure–activity relationships for quinolone derivatives. 65 Among the synthesized quinolone derivatives by Wang and coworkers, compounds 161a and 162b displayed selective antiviral activity (ED 50 0.65–9.5 μg mL −1 ) against HIV in acutely infected H9 lymphocytes with therapeutic indexes in the range of 0.6–5.7. Compound 161b , bearing acetoxy groups on both the 6- and 7-positions, was the most active (ED 50 value, 0.65 μg mL −1 ) with a therapeutic index of about 5.…”