The discovery of novel sanjuanolide derivatives as chemotherapeutic agents targeting castration-resistant prostate cancer.
The discovery of novel sanjuanolide derivatives as chemotherapeutic agents targeting castration-resistant prostate cancer.
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发现新型三胡内酯衍生物作为针对去势抵抗性前列腺癌的化疗药物。
DOI：
10.1016/j.bioorg.2021.104880
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发表时间：
2021-03
影响因子：
5.1
通讯作者：
Zheng Xiaohui
中科院分区：
文献类型：
--
作者：
Wang Guangbao;Chen Xiaojing;Wang Nan;Xiao Yunbei;Shu Sheng;Alsayed Ali Mohammed Mohammed;Liu Lu;Ma Yue;Liu Peng;Zhang Qianwen;Chen Xiangjuan;Liu Zhiguo;Zheng Xiaohui
仍然迫切需要更有效的治疗去势抵抗性前列腺癌（CRPC）的疗法，CRPC是前列腺癌患者死亡的主要原因。本研究设计、合成了一系列具有潜在抗CRPC活性的圣胡安碱衍生物。大多数化合物对CRPC细胞具有良好的选择性，IC 50值< 20 µM。此外，观察到对人正常肝MIHA细胞和正常前列腺基质肌成纤维细胞WPMY-1细胞的最小副作用，IC 50> 100 µM。代表性化合物S 07可减慢CRPC细胞的增殖速率，促进细胞凋亡，并导致G2/M期细胞聚集，G1/G 0期细胞减少。进一步的机制研究表明，S 07处理引发了强烈的DNA损伤，并以剂量依赖的方式引起了强烈的DNA损伤反应。这些结果表明，圣胡安碱衍生物，特别是S 07，通过引发强烈的DNA损伤和DNA损伤反应，选择性地诱导CRPC细胞死亡。
There remains a critical need for more effective therapies for the treatment of castration-resistant prostate cancer (CRPC), which is the leading cause of death in patients with prostate cancer. In this study, a series of sanjuanolide derivatives were designed, synthesized and evaluated as potential anti-CRPC agents. Most of the compounds had excellent selectivity for CRPC cells withIC50values < 20 µM. Moreover, minimal side effects on human normal hepatic MIHA cells and normal prostatic stromal myofibroblast WPMY-1 cells were observed, withIC50> 100 µM. The representative compoundS07slowed down the proliferative rate of CRPC cells, promoted cell apoptosis and caused G2/M phase accumulation, as well as G1/G0 phase reduction. Further mechanistic studies showed that S07treatment triggered intense DNA damage and provoked strong DNA damage response in a dose-dependent manner. These findings suggested that sanjuanolide derivatives, especiallyS07,selectively induced CRPC cell death by triggering intense DNA damage and DNA damage response.
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影响因子：
4
作者：
Xiao-Hui Zheng;Y. Zhong;Cai-Ping Tan;L. Ji;Z. Mao
通讯作者：
Xiao-Hui Zheng;Y. Zhong;Cai-Ping Tan;L. Ji;Z. Mao
影响因子：
14.8
作者：
Olive, Peggy L.;Banath, Judit P.
通讯作者：
Banath, Judit P.
影响因子：
4.8
作者：
Boulares, AH;Yakovlev, AG;Smulson, M
通讯作者：
Smulson, M
影响因子：
5.1
作者：
Shaffer CV;Cai S;Peng J;Robles AJ;Hartley RM;Powell DR;Du L;Cichewicz RH;Mooberry SL
通讯作者：
Mooberry SL
影响因子：
2.6
作者：
S. Hotte;F. Saad
通讯作者：
S. Hotte;F. Saad