ANTITUMOR DRUG DESIGN - DNA-BINDING LIGANDS, WHICH INHIBIT THE TOPOISOMERASE-I

DNA-enzymes, which are overexpressed in special tumour cells represent in general interesting targets for an antitumour drug design. In this context a survey about the function and the biochemical mechanistic a spects of topoisomerases is given. In the last years detailed studies in medicinal chemistry (structure activity relationships) revealed tha t first of all topoisomerase I inhibitor will become an attractive cla ss of promising and perhaps more selective drugs in cancer chemotherap y. Thus, in the present review actual aspects about drug design develo pments of topoisomerase I inhibitors are presented. Moreover some rece nt results about new lead substances, some structure activity relation ships and some clinical aspects are discussed.