TAN-20

• 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-20
• 英文别名: 5,17,17-Trimethyl-9-(3-nitrophenyl)-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-heptaene；5,17,17-trimethyl-9-(3-nitrophenyl)-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-heptaene
• 化学式: C₂₆H₂₃N₃O₃
• 分子量: 425.487
• InChiKey: QOGXRCLSEMFIDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  32
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  87.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  丹参酮 IIA 、 间硝基苯甲醛 在 ammonium acetate 作用下， 以 溶剂黄146 为溶剂， 生成 TAN-20
  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

• Tanshinone-IIA-Based Analogues of Imidazole Alkaloid Act as Potent Inhibitors To Block Breast Cancer Invasion and Metastasis in Vivo
  作者：Qiong Wu、Kangdi Zheng、Xiaoting Huang、Li Li、Wenjie Mei

  DOI：10.1021/acs.jmedchem.8b01018

  日期：2018.12.13

  Tanshinone-IIA (Tan-IIA), a primary active component extracted from commonly used Chinese herbal, Salvia miltiorrhiza (Danshen), is considered as a potential inhibitor against tumor cell proliferation. However, the potential application of Tan-IIA is hindered by its poor water solubility and low bioavailability. In this work, an imidazole moiety was linked to the skeleton of Tan-IIA to enhance its antitumor activity. A series of Tan-IIA-based analogues TA01-TA12 were synthesized, and their inhibitory activities against the migration and invasion of MDA-MB-231 cells were investigated. All compounds, particularly TA12, markedly inhibited the proliferation, migration, and invasion of MDA-MB-231cells. TA12 also prominently blocked cancer cell metastasis in blood vessels and surrounding tissues in zebrafish xenograft model. Further studies showed that the mechanisms may involve S-phase arrest pathway, which was probably caused by inducing reactive oxygen species production and activating DNA damage. These results indicated that the Tan-IIA-based analogues of imidazole derivates can act as potent antimetastasis agents.
• 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.