title: Synthesis, molecular modelling, and antiproliferative and cytotoxic effects of carbocyclic derivatives of distamycin with chlorambucil moiety.
abstract: New carbocylic analogues of distamycin and netropsin with chlorambucil moieties 5-8 have been synthesised. Data from the ethidium displacement assay showed that these compounds bind in the minor groove of DNA. The observed reduced affinity to AT pairs and increased affinity towards GC sequences of the carbocyclic lexitropsins with chlorambucil moiety 5-8 in comparison with netropsin and distamycin was observed and rationalised by means of molecular modelling techniques. All of the compounds 5-8 showed antiproliferative and cytotoxic effects in the standard cell line of the mammalian tumour MCF-7.
authors.affiliation: Department of Organic Chemistry, Medical Academy of Białystok, Mickiewicza 2c, 15-230 Białystok, Poland. dbartule@amb.ac.bialystok.pl
authors.forename: D
authors.initials: D
authors.lastname: Bartulewicz
authors.forename: K
authors.initials: K
authors.lastname: Bielawski
authors.forename: A
authors.initials: A
authors.lastname: Bielawska
authors.forename: A
authors.initials: A
authors.lastname: Rózański
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D004214:Distamycins / Q000737:chemistry*; D015195:Drug Design; D004996:Ethidium / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004214:Distamycins; D002699:Chlorambucil; C030000:stallimycin; D004247:DNA; D004996:Ethidium