The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected human cell systems, was found to suppress the integration of proviral DNA into the cellular DNA genome. In the present study 2 was tested with purified HIV-1 integrase and found to be inactive in the cleavage (3'-processing) and integration (strand transfer) assays. However, the semisynthetic 3-O-demethylated congener 9 characterized by a catechol substructure exhibited remarkable activities in both assays. Structure-activity relationship studies with 30 natural (1-6), semisynthetic (7-21), and synthetic (37-43, 45, 46) lignans revealed that (1) the lactone moiety is crucial since compounds with a butane-1,4-diol or tetrahydrofuran substructure and also lignanamide analogues lacked activity and (2) the number and arrangement of phenolic hydroxyl groups is important for the activity of lignanolides. The congener with two catechol substructures (7) was found to be the most active compound in this study. 7 was also a potent inhibitor of the "disintegration" reaction which models the reversal of the strand transfer reaction. The inhibitory activity of 7 with the core enzyme fragment consisting of amino acids 50-212 suggests that the binding site of 7 resides in the catalytic domain.

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The coumarin patterns of Pelargonium sidoides DC. and Pelargonium reniforme CURT., forming the origin of the herbal medicine “umckaloabo”, were analysed and compared for therapeutic equivalence. For both species, members of tri- and tetraoxygenated coumarins almost exclusively were present in the respective metabolic pools. However, the roots of P. sidoides and P. reniforme expressed conspicuously distinct coumarin variations, with umckalin, its 7-O-methyl ether, 7-acetoxy-5,6-dimethoxycoumarin, 6,8-dihydroxy-7-methoxycoumarin, 6,8-dihydroxy-5,7-tetramethoxycoumarin, artelin and three unique coumarin sulfates as uncommon metabolites of this class of secondary products of P. sidoides. Furthermore, the highly oxygenated but known coumarins fraxinol, isofraxetin and fraxidin were associated with the new 8-hydroxy-5,6,7-trimethoxycoumarin as representatives of P. reniforme. Of the twelve identified coumarins only the two species shared the ubiquitous scopoletin and the unique 6,7,8-trihydroxycoumarin. From the oxygenation patterns it is evident that the majority of these Pelargonium coumarins match the recently established basic structural requirements for marked antibacterial activity, i.e. the presence of a methoxy function at C-7 and an OH group at either the C-6 or C-8 position. The current data on the coumarin profiles of each Pelargonium species also indicate a previous erroneous identification of the plant material claimed to be P. reniforme. Absence and presence of umckalin and its 7-O-methyl ether defines P. reniforme and P. sidoides, respectively.

A proline-free ergopeptine-type alkaloid, ergobalansinine [1], and three simple ergoline alkaloids, chanoclavine-I, ergine, and lysergic acid -hydroxyethylamide, were isolated from the seeds of Ipomoea piurensis. The structure of 1 was established on the basis of spectral data. All compounds are also present in the other epigeal parts in contrast to the roots.

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