Design, synthesis, and evaluation of DNA topoisomerase II-targeted nucleosides.
We developed novel nucleoside-based topoisomerase II selective inhibitors and showed that small structural units, such as catechols, are essential for DNA topoisomerase II inhibitory activity. Moreover, nucleoside analogues containing TBS and 1,3-dithian moieties had potent and selective DNA topoisomerase II inhibitory activities. In further experiments, compound 25b having a beta configuration of the thymine moiety showed relatively strong growth inhibitory activity against cancer cell lines, and was more potent against all cancer cell lines than compound 26b, which carries a thymine moiety in the alpha configuration.
['Matsumoto|Hironobu|H|', 'Yamashita|Mitsuaki|M|', 'Tahara|Teruyuki|T|', 'Hayakawa|Shinya|S|', 'Wada|Shun-Ichi|SI|', 'Tomioka|Kiyoshi|K|', 'Iida|Akira|A|']
D066241:Carbon-13 Magnetic Resonance Spectroscopy D045744:Cell Line, Tumor D015195:Drug Design D004354:Drug Screening Assays, Antitumor D006801:Humans D013058:Mass Spectrometry D009711:Nucleotides D066244:Proton Magnetic Resonance Spectroscopy D013055:Spectrophotometry, Infrared D059005:Topoisomerase II Inhibitors
DNA topoisomerase Nucleoside Cancer Antiproliferative activity