14-methyl-10,12-dinitro-8,13,13b,14-tetrahydroindolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5(7H)-one | 1355077-90-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 14-methyl-10,12-dinitro-8,13,13b,14-tetrahydroindolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5(7H)-one
• 英文别名: 10,12-Dinitroevodiamine；21-methyl-5,7-dinitro-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4(9),5,7,15,17,19-heptaen-14-one
• CAS: 1355077-90-5
• 化学式: C₁₉H₁₅N₅O₅
• 分子量: 393.359
• InChiKey: MNEKLQPLEVYQNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  吴茱萸碱 在 硫酸 、 potassium nitrate 作用下， 反应 12.0h， 以58.1%的产率得到14-methyl-10,12-dinitro-8,13,13b,14-tetrahydroindolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5(7H)-one
  参考文献：
  名称：

  New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations

  摘要：

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.

  DOI：

  10.1021/jm300605m

文献信息

• An A-ring substituted evodiamine derivative with potent anticancer activity against human non-small cell lung cancer cells by targeting heat shock protein 70
  作者：Hye-Young Min、Yijae Lim、Hyukjin Kwon、Hye-Jin Boo、Seung Yeob Hyun、Junhwa Hong、Suckchang Hong、Ho-Young Lee

  DOI：10.1016/j.bcp.2023.115507

  日期：2023.5
• ANTI-CANCER PHARMACEUTICAL COMPOSITION FOR TARGETING HEAT SHOCK PROTEIN 70, CONTAINING INDOLOQUINAZOLIDINE ALKALOID
  申请人：SEOUL NATIONAL UNIVERSITY R & DB FOUNDATION

  公开号：US20240140949A1

  公开（公告）日：2024-05-02

  The present invention relates to: an anti-cancer pharmaceutical composition for targeting heat shock protein 70, containing an indoloquinazolidine alkaloid; and the like. The indoloquinazolidine alkaloid of the present invention inhibits the growth of tumors and inhibits the expression of HSP70 protein and the colony formation activity of cancer cells, and inhibits the growth of tumors in mouse models with xenografts of a cancer cell line and xenografts of patient-derived cancer, and inhibits the growth of cancer cells resistant to drugs such as pemetrexed, cisplatin, and paclitaxel, and thus is expected to be widely usable in the prevention and treatment of various types of cancer.
• New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations
  作者：Guoqiang Dong、Shengzheng Wang、Zhenyuan Miao、Jianzhong Yao、Yongqiang Zhang、Zizhao Guo、Wannian Zhang、Chunquan Sheng

  DOI：10.1021/jm300605m

  日期：2012.9.13

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.