Synthesis, molecular modelling, and antiproliferative and cytotoxic effects of carbocyclic derivatives of distamycin with chlorambucil moiety

New carbocylic analogues of distamycin and netropsin with chlorambucil moie ties 5-8 have been synthesised. Data from the ethidium displacement assay s howed that these compounds bind in the minor groove of DNA. The observed re duced affinity to AT pairs and increased affinity towards GC sequences of t he carbocyclic lexitropsins with chlorambucil moiety 5-8 in comparison with netropsin and distamycin was observed and rationalised by means of molecul ar modelling techniques. All of the compounds 5-8 showed antiproliferative and cytotoxic effects in the standard cell line of the mammalian tumour MCF -7. (C) 2001 Editions scientifiques et medicales Elsevier SAS.