Aromatic analogues of DNA minor groove binders--synthesis and biological evaluation.
Nine carbocyclic analogues of mono- and bis-lexitropsins and two analogues of pentamidine with unsubstituted N-terminal amine group were synthesized. We have investigated the cytotoxic activity of new aromatic analogues of DNA binding ligands in MCF-7 breast cancer cells and assessed their ability to act as inhibitors of topoisomerase I and II. These studies indicate that aromatic analogues of bis-netropsin contain two identical units tethered by alkyloxyl chains are a potent catalytic inhibitor of both topoisomerases and exhibit moderate cytotoxicity in MCF-7 breast cancer cells.
Department of Organic Chemistry, Medical University of Białystok, A. Mickiewicza 2a, 15-222 Białystok, Poland. pucanka@amb.edu.pl
Anna
A
Pućkowska
Krzysztof
K
Bielawski
Anna
A
Bielawska
Krystyna
K
Midura-Nowaczek
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006690:Bisbenzimidazole / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009429:Netropsin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D010419:Pentamidine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D008024:Ligands; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D009429:Netropsin; D010419:Pentamidine; D004247:DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D006690:Bisbenzimidazole