Novel quinolone-3-carboxylic acid derivatives as anti-HIV-1 agents: design, synthesis, and biological activities

A new series of quinolone-3-carboxylic acids featuring different hydrophobic groups at N-1, C-2, C-7, and C-8 positions were synthesized and evaluated for their activity against single-cycle replicable HIV NL4-3 as inhibition rate of p(24) expression in Hela cells cultures. Most of the synthesized compounds showed anti-HIV activity with no significant cytotoxicity at concentration of 100 mu M. The most active compounds 4h, 4k, and 4j exhibited anti-HIV activity with an inhibition rate of 55, 71, and 84 %, respectively. A docking study using the crystallographic data available for PFV integrase including its complexes with Mg2+ and Raltegravir revealed that the active compounds could occupy same space near Raltegravir and interact with the Mg-2 (+) ions in the active site. Thus, the anti-HIV activity of the synthesized compounds might involve a metal chelating mechanism. [GRAPHICS] .