Synthesis-Enabled Probing of Mitosene Structural Space Leads to Improved IC50 over Mitomycin C.
- Resource Type
- Article
- Authors
- Zheng, Zhitong; Touve, Mollie; Barnes, Josue; Reich, Norbert; Zhang, Liming
- Source
- Angewandte Chemie. Aug2014, Vol. 126 Issue 35, p9456-9459. 4p.
- Subject
- *MITOMYCIN C
*DNA
*ALKYLATION
*CYCLOPROPANE
*PROSTATE cancer treatment
- Language
- ISSN
- 0044-8249
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]