Synthesis-enabled probing of mitosene structural space leads to improved IC₅₀ over mitomycin C.
Synthesis-enabled probing of mitosene structural space leads to improved IC₅₀ over mitomycin C.
复制标题
丝裂霉素结构空间的合成探测可提高 IC 值（优于丝裂霉素 C）。
DOI：
10.1002/anie.201402268
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Zhang,Liming
中科院分区：
文献类型：
--
作者：
Zheng,Zhitong;Touve,Mollie;Barnes,Josue;Reich,Norbert;Zhang,Liming
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.
