title: Design, synthesis, DNA-binding and cytotoxicity evaluation of new potential combilexines.
abstract: Combilexines, compounds in which a DNA intercalator is linked to a minor groove binding component, interact with the DNA in a sequence specific manner to yield in most cases compounds with anticancer activity. A series of new compounds closely related to netropsin in which the two components were linked by an amide group was synthesised as potential combilexines. As some of these compounds showed cytotoxic activity in vitro, an attempt was made to rationalise their mechanism of action. The DNA binding characteristics of the carboxamides were evaluated by thermal denaturation experiments and by ethidium bromide displacement assay. Their ability to inhibit the topoisomerase I was also determined. It was concluded that the new compounds were only weak DNA ligands although able in some cases to inhibit topoisomerase I.
authors: Department of Pharmacy, Johannes Gutenberg University, Staudingerweg 5, D-55099 Mainz, Germany.
authors: Christian
authors: C
authors: Hotzel
authors: Annalisa
authors: A
authors: Marotto
authors: Ulf
authors: U
authors: Pindur
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D009691:Nucleic Acid Denaturation; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007364:Intercalating Agents; D059004:Topoisomerase I Inhibitors; D004247:DNA