1. Synthesis-Enabled Probing of Mitosene Structural Space Leads to Improved IC50 over Mitomycin C.
- Author
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Zheng, Zhitong, Touve, Mollie, Barnes, Josue, Reich, Norbert, and Zhang, Liming
- Subjects
DNA analysis ,ALKYLATION kinetics ,MITOMYCIN C ,CYCLOPROPANE ,PROSTATE cancer treatment - Abstract
A DNA crosslinking approach, which is distinct but related to the double alkylation by mitomycin C, involving a novel electrophilic spiro-cyclopropane intermediate is hypothesized. Rational design and substantial structural simplification permitted the expedient chemical synthesis and rapid discovery of MTSB-6, a mitomycin C analogue which is twice as potent as mitomycin C against the prostate cancer cells. MTSB-6 shows improvements in its selective action against noncancer prostate cells over mitomycin C. This hypothesis-driven discovery opens novel yet synthetically accessible mitosene structural space for discovering more potent and less toxic therapeutic candidates. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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