Seventeen lichen acids comprising despides, 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 microM; 15 were below 50 microM. Several of these compounds were also examined for their activity against HIV-2 integrase and mammalian topoisomerase I.

Separation of metabolites of Penicillium vermiculatum DANG present in the cultivation medium afforded three new antibiotics; vermiculinel), vermistatin2) and vermicillin3) . The structure of vermiculine, a macrolide dilactone has already been solved by X-ray diffraction analysis". This paper presents the structure elucidation of the second compound of this series, vermistatin.In our previous paper2) we reported the isolation, antibiotic and cytotoxic activity of vermistatin (1); it is a white crystalline compound of molecular formula C,,H,,O, (328

VermixocinsA and B, 3-(r-hydroxy-3'-methylbutyl)-and 3-(r-acetoxy-3'-methylbutyl)-l lhydroxy-4-methoxy-9-methyl-5//,7/f-dibenzo [c,/] respectively. A new strain, specified B 5, selected from the above mentioned parental strain formed dehydroaltenusin only4). This compoundin addition to other polyketide metabolites was isolated from the mycelium of T. flavus (ATCC52201) grown on a malt extract medium5). Two new minor metabolites designated vermixocins A (1) and B (2) were found in the mycelium of P. vermiculatum cultivated under conditions optimized for vermiculin production. The structure elucidation of compounds1 and 2 is the subject of this report.

A mixture of related metabolites (denoted OR-1) was isolated from the fermentation broth of Penicillium funiculosum together with mitorubrinic acid. Structurally OR-1 is glyceric acid esterified with C14-C18 fatty acids. Steady-state studies revealed that OR-1 behaved like an uncompetitive trypsin inhibitor with Ki 17.6 mumol/L.