DEPSIDES AND DEPSIDONES AS INHIBITORS OF HIV-1 INTEGRASE - DISCOVERY OF NOVEL INHIBITORS THROUGH 3D DATABASE SEARCHING

Seventeen lichen acids comprising depsides, depsidones, and their synt hetic derivatives have been examined fur their inhibitory activity aga inst HIV-1 integrase, and two pharmacophores associated with inhibitio n 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 w ere assayed for HIV-1 integrase inhibition, and of these, 27 had inhib itory IC50 values of less than 100 mu M; 15 were below 50 mu M. Severa l of these compounds were also examined for their activity against HIV -2 integrase and mammalian topoisamerase I.