TAN-25

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: TAN-25
• 英文别名: 2-methoxy-5-(4,9,9-trimethyl-9,10,11,12-tetrahydro-1H-furo[2',3':1,2]phenanthro[3,4-d]imidazol-2-yl)phenol；2-methoxy-5-(5,17,17-trimethyl-3-oxa-8,10-diazapentacyclo[10.8.0.02,6.07,11.013,18]icosa-1(12),2(6),4,7(11),9,13(18),19-heptaen-9-yl)phenol
• 化学式: C₂₇H₂₆N₂O₃
• 分子量: 426.515
• InChiKey: GIRNIZRQUPIPBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  71.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  异香兰素 、 丹参酮 IIA 在 ammonium acetate 作用下， 以 溶剂黄146 为溶剂， 生成 TAN-25
  参考文献：
  名称：

  Synthesis of novel tanshinone derivatives for treatment of castration‐resistant prostate cancer

  摘要：

  AbstractProstate cancer is the second leading cause of death in USA and has developed serious resistance to current drugs. Thus, development of new drugs for the treatment of castration‐resistant prostate cancer (CRPC) is urgently needed. In this study, 25 novel derivatives of tanshinone IIA as potential androgen receptor (AR) suppression reagents for the treatment of CRPC have been synthesized. The inhibition on DHT‐mediated AR transactivation and cell viability assay were performed to test the synthesized compounds. The results showed that among 25 new compounds, seven methoxy‐substituted tanshinone IIA derivatives showed significant inhibition effect on DHT‐mediated AR transactivation. In particular, TAN‐24 that contains three methoxy groups showed the strongest inhibition effect on DHT‐mediated AR transactivation. In addition, TAN‐24 also suppressed DHT‐AR transactivation more effectively than those of tanshinoneIIA and enzalutamide. In cytotoxicity against human prostate cancer cell lines assay, TAN‐24 exhibited the most potent in vitro cytotoxicity against LNCaP and CWR22Rv1 cells, with IC50 values 20‐ and 19‐times lower than those of tanshinone IIA and comparable to enzalutamide. TAN‐24 reported in the present work represents a novel and effective AR suppression drug, showing great potential for the treatment of CRPC.

  DOI：

  10.1111/cbdd.13567

文献信息

• Synthesis of novel tanshinone derivatives for treatment of castration‐resistant prostate cancer
  作者：Defeng Xu、Hang Hu、Jing Guan、Jun Da、Yipeng Xie、Yalin Liu、Ren Kong、Guoqiang Song、Huan Zhou

  DOI：10.1111/cbdd.13567

  日期：2019.9

  AbstractProstate cancer is the second leading cause of death in USA and has developed serious resistance to current drugs. Thus, development of new drugs for the treatment of castration‐resistant prostate cancer (CRPC) is urgently needed. In this study, 25 novel derivatives of tanshinone IIA as potential androgen receptor (AR) suppression reagents for the treatment of CRPC have been synthesized. The inhibition on DHT‐mediated AR transactivation and cell viability assay were performed to test the synthesized compounds. The results showed that among 25 new compounds, seven methoxy‐substituted tanshinone IIA derivatives showed significant inhibition effect on DHT‐mediated AR transactivation. In particular, TAN‐24 that contains three methoxy groups showed the strongest inhibition effect on DHT‐mediated AR transactivation. In addition, TAN‐24 also suppressed DHT‐AR transactivation more effectively than those of tanshinoneIIA and enzalutamide. In cytotoxicity against human prostate cancer cell lines assay, TAN‐24 exhibited the most potent in vitro cytotoxicity against LNCaP and CWR22Rv1 cells, with IC50 values 20‐ and 19‐times lower than those of tanshinone IIA and comparable to enzalutamide. TAN‐24 reported in the present work represents a novel and effective AR suppression drug, showing great potential for the treatment of CRPC.