Design, synthesis and docking studies of new 4-hydroxyquinoline-3-carbohydrazide derivatives as anti-HIV-1 agents.

A new class of 4-hydroxyquinoline-3-carbohydrazide derivatives was prepared and evaluated for its anti-HIV activity. The primary bioassay results indicated that most of tested compounds possess moderate inhibitory properties against HIV-1 virus (NL4-3) in Hela cells cultures. Our results also indicated that compounds 6d and 7e were the most potent anti-HIV agents among the synthesized compounds with inhibition rate of 32 and 28% at concentration of 100 μM, respectively. A docking study using the later crystallographic data available for PFV integrase including its complexes with Mg2+ and raltegravir, showed that the designed compounds bind into the active site of integrase such that carboxylic and hydroxyl groups of 4-hydroxyquinoline-3-carbohydrazide chelate the Mg2 + ion. Interestingly, all of the synthesized compounds were found to present no significant cytotoxicity at concentration of 100 μM. Therefore, these compounds can provide a very good basis for the development of new anti-HIV-1 agents. © Georg Thieme Verlag KG Stuttgart · New York.