Depsides and Depsidones as Inhibitors of HIV-1 Integrase: Discovery of Novel Inhibitors through 3D Database Searching

Abstract

Seventeen lichen acids comprising depsides, depsidones, and their synthetic derivatives have been examined for their inhibitory activity against HIV-1 integrase, and two pharmacophores associated with inhibition of this enzyme have been identified. A search of the NCI 3D database of approximately 200 000 structures yielded some 800 compounds which contain one or the other pharmacophore. Forty-two of these compounds were assayed for HIV-1 integrase inhibition, and of these, 27 had inhibitory IC₅₀ values of less than 100 μM; 15 were below 50 μM. Several of these compounds were also examined for their activity against HIV-2 integrase and mammalian topoisomerase I.