Synthesis, biological evaluation, and structure-activity relationships of dithiolethiones as inducers of cytoprotective phase 2 enzymes.
Synthesis, biological evaluation, and structure-activity relationships of dithiolethiones as inducers of cytoprotective phase 2 enzymes.
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DOI：
10.1021/jm100425v
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发表时间：
2010-06-24
影响因子：
7.3
通讯作者：
Babu J
中科院分区：
文献类型：
--
作者：
Munday R;Zhang Y;Paonessa JD;Munday CM;Wilkins AL;Babu J
Dithiolethiones are a family of promising cancer chemopreventive agents, and induction of Phase 2 enzymes is key to their chemopreventive activities. Two dithiolethiones have been evaluated in humans for cancer prevention. While some chemopreventive activities were detected in several human studies, potential side effects are a concern. Herein, we report structure-activity relationships of 25 dithiolethiones. Several compounds show exceedingly potent and bladder specific activity in Phase 2 enzyme induction. Structural features responsible for such activity, as well as those inhibiting the activity, are discussed. Moreover, the compounds activate and depend on Nrf2 for their inductive activities. Nrf2 is a major transcriptional stimulator of cytoprotective genes and is critical for cancer prevention. Thus, several new dithiolethiones that are highly promising for bladder cancer prevention have been identified. Because the compounds act specifically in the bladder, the likelihood of potential systemic toxicity may be low.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
2.9
作者：
Munday, Rex;Zhang, Yuesheng;Stephenson, Katherine K.
通讯作者：
Stephenson, Katherine K.
影响因子：
3.8
作者：
BONA, M;BOUDEVILLE, P;BURGOT, JL
通讯作者：
BURGOT, JL
DOI：
10.1002/cber.19510840507
发表时间：
1951-01-01
期刊：
CHEMISCHE BERICHTE-RECUEIL
影响因子：
--
作者：
BOTTCHER, B;BAUER, F
通讯作者：
BAUER, F
DOI：
10.1097/00008571-199706000-00008
发表时间：
1997-06-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Schulz, WA;Krummeck, A;Sies, H
通讯作者：
Sies, H