Design, synthesis, and evaluation of DNA topoisomerase II-targeted nucleosides

Publication date: 1 August 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 15
Author(s): Hironobu Matsumoto, Mitsuaki Yamashita, Teruyuki Tahara, Shinya Hayakawa, Shun-ichi Wada, Kiyoshi Tomioka, Akira Iida
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.

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