5-acetoxyisogoniothalamin oxide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 5-acetoxyisogoniothalamin oxide
• 英文别名: cheliensisin A；[(2R,3S)-6-oxo-2-[(2S,3R)-3-phenyloxiran-2-yl]-2,3-dihydropyran-3-yl] acetate
• 化学式: C₁₅H₁₄O₅
• 分子量: 274.273
• InChiKey: AHZVYVPVHRHEHF-MYPMTAMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-acetoxyisogoniothalamin oxide 在 三氟化硼乙醚 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 反应 4.75h， 生成 2(E)-styryl-4-[(5'S,6'R)-5'-acetoxyl-5',6'-dihydro-2'H-pyran-2'-one-6'-yl]-5-phenyl-oxazole
  参考文献：
  名称：

  Development of novel conformation-constrained cytotoxic derivatives of cheliensisin A by embedment of small heterocycles

  摘要：

  Cheliensisin A is a natural styryl-lactone isolated from Goniothalamus cheliensis Hu in considerably large quantity with putative anticancer activities. However, its poor water solubility and chemical instability have precluded cheliensisin A as a potential drug candidate. To explore the strategy to overcome these problems, 21 novel derivatives of cheliensisin A with different substitutions at C-7 and C-8 positions were designed and synthesized. Inhibition of proliferation against five tumors cell lines indicates that eight new derivatives with embedment of oxazole or oxazoline exhibit improved cytotoxicity on SK-BR-3 and PANC-1, and compounds 2d and 2g show 5-8 folds higher potency than cisplatin. HPLC investigation of representative compounds indicates that oxazole and oxazoline analogs exhibit much improved chemical stability than their natural parent. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.028

文献信息

• [EN] HETEROCYCLO COMPOUNDS AS APOPTOTIC INDUCERS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS COMME INDUCTEURS D'APOPTOSE ET LEURS UTILISATIONS
  申请人：KUNMING INST BOTANY CN ACAD

  公开号：WO2014117741A1

  公开（公告）日：2014-08-07

  Disclosed are heterocyclo compounds that have a formula represented by the following: and wherein X, R1, R2, R3, R4, R5, R6, and n are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of cancer conditions in mammals including humans, including by way of non-limiting example, prostate, colon, bladder, melanoma, liver, breast, cervical, ovarian, esophagi, glialblastoma, pancreatic and lung cancer.

  本公开揭示了具有以下表示的化学式的杂环化合物：其中X，R1，R2，R3，R4，R5，R6和n如本文所述。这些化合物可以制备为药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的多种癌症病况，例如前列腺癌、结肠癌、膀胱癌、黑色素瘤、肝癌、乳腺癌、宫颈癌、卵巢癌、食管癌、神经胶质母细胞瘤、胰腺癌和肺癌等。
• New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer
  作者：Xiaohui Hua、Jiheng Xu、Xu Deng、Jiawei Xu、Jingxia Li、David Q. Zhu、Junlan Zhu、Honglei Jin、Zhongxian Tian、Haishan Huang、Qin-shi Zhao、Chuanshu Huang

  DOI：10.1016/j.canlet.2018.08.013

  日期：2018.11

  ChlA-F is a novel conformation-derivative of Cheliensisin A, styryl-lactone isolates that show potent anti-tumor potential in vivo and vitro. However, the anti-cancer activity and its potential mechanisms underlying ChlA-F action have never been explored. In the present study, we evaluated the potency of ChlA-F on autophagy-mediated anchorage-independent growth inhibition in human high-grade invasive bladder cancer (BC) cells. We found that ChlA-F treatment significantly inhibited anchorage-independent growth of human BC cells by inducing autophagy in a Sestrin-2 (SESN2)-dependent fashion. Our results revealed that ChlA-F treatment specifically induced SESN2 expression via increasing its transcription and mRNA stability. On one hand, ChlA-F treatment markedly attenuated Dicer protein abundance, in turn abolishing miR-27a maturation and further relieving miR-27a binding directly to SESN2 mRNA 3'UTR, thereby promoting SESN2 mRNA stabilization. On the other hand, ChlA-F treatment promoted Sp1 abundance and consequently mediated SESN2 transcription. These results demonstrate that its activation of the autophagic pathway through specifically promoting SESN2 expression mediates the anti-cancer effect of ChlA-F, which offers insights into the novel anti-cancer effect of ChlA-F on BC, as well as providing therapeutic alternatives against human BC.
• HETEROCYCLO COMPOUNDS AS APOPTOTIC INDUCERS AND USES THEREOF
  申请人：KUNMING INSTITUTE OF BOTANY, CHINESE ACADEMYOF SCIENCES

  公开号：US20150361062A1

  公开（公告）日：2015-12-17

  Disclosed are heterocyclo compounds that have a formula represented by the following: and wherein X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and n are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of cancer conditions in mammals including humans, including by way of non-limiting example, prostate, colon, bladder, melanoma, liver, breast, cervical, ovarian, esophagi, glialblastoma, pancreatic and lung cancer.
• US9682947B2
  申请人：——

  公开号：US9682947B2

  公开（公告）日：2017-06-20
• Development of novel conformation-constrained cytotoxic derivatives of cheliensisin A by embedment of small heterocycles
  作者：Xu Deng、Jia Su、Yu Zhao、Li-Yan Peng、Yan Li、Zhu-Jun Yao、Qin-Shi Zhao

  DOI：10.1016/j.ejmech.2011.06.028

  日期：2011.9

  Cheliensisin A is a natural styryl-lactone isolated from Goniothalamus cheliensis Hu in considerably large quantity with putative anticancer activities. However, its poor water solubility and chemical instability have precluded cheliensisin A as a potential drug candidate. To explore the strategy to overcome these problems, 21 novel derivatives of cheliensisin A with different substitutions at C-7 and C-8 positions were designed and synthesized. Inhibition of proliferation against five tumors cell lines indicates that eight new derivatives with embedment of oxazole or oxazoline exhibit improved cytotoxicity on SK-BR-3 and PANC-1, and compounds 2d and 2g show 5-8 folds higher potency than cisplatin. HPLC investigation of representative compounds indicates that oxazole and oxazoline analogs exhibit much improved chemical stability than their natural parent. (C) 2011 Elsevier Masson SAS. All rights reserved.