DNA minor-groove binders: results and design of new antitumor agents

DNA minor-groove binding drugs have been extensively studied in the last ye ars in order to influence the regulation of gene expression in neoplastic d isorders by means of specific interactions with DNA bases. Pyrrolo[2,1-c][1 ,4]benzodiazepines (PBDs), CC-1065 and distamycins are three classes of min or-groove alkylating agents which showed interesting cytotoxicity profiles, but they cannot be used in humans for various toxicity problems. For this reason many groups applied heterocyclic substitutions extensively, in order to either modify the reactivity profile or introduce extra interactions wi thin the minor groove, thus changing the binding site or modulating the bin ding sequence. (C) 1999 Elsevier Science S.A. All rights reserved.