Chemistry and biological activity of rocaglamide derivatives and related compounds in Aglaia species (Meliaceae)

The genus Aglaia is the source of a unique group of natural products featur ing a cyclopenta[b]tetrahydrobenzofuran skeleton. Commonly these compounds, which until now include more than 50 naturally occurring derivatives, are named after the parent compound, rocaglamide, which was described for the f irst time almost twenty years ago. This review highlights the chemical dive rsity of rocaglamide derivatives and of biogenetically similar compounds fr om the genus Aglaia and their remarkable biological activity in the fields of insecticides and cytostatic agents. With a few exceptions, all naturally occurring rocaglamide derivatives exhibit striking insecticidal activity a gainst various pest insects. In addition, they display pronounced cytostati c activity against human cancer cell lines in vitro. Furthermore, it was sh own recently that rocaglamide and several of its congeners inhibit NF-kappa B induced gene activation in human T cells and are able to elicit apoptosis in resistant tumor cells. Taken together, these data make rocaglamide deri vatives interesting candidates for possible therapeutic agents primarily in the field of cancer chemotherapy. In some Aglaia species, rocaglamide deri vatives co-occur with biogenetically similar natural products of the aglain , aglaforbesin or forbaglin type. These latter compounds differ from rocagl amide and its congeners mainly by the nature of their heterocycle. Furtherm ore, they seem to be devoid of significant biological activity at least in the areas mentioned above, thereby pointing to the cyclopenta[b]tetrahydrob enzofuran core of the rocaglamide skeleton as one essential structural requ irement for the pronounced biological activity of the rocaglamides.