2-acetyl-3-hydroxy-5-methoxy-4,4,6-tripropylcyclohexa-2,5-dienone | 946148-02-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-acetyl-3-hydroxy-5-methoxy-4,4,6-tripropylcyclohexa-2,5-dienone
• CAS: 946148-02-3
• 化学式: C₁₈H₂₈O₄
• 分子量: 308.418
• InChiKey: WWGIVCSYCQSISR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.26
• 重原子数：
  22.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-acetyl-3-hydroxy-5-methoxy-4,4,6-tripropylcyclohexa-2,5-dienone 在 硫酸 、 碘 、 三溴化硼 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 2-(naphthalen-1'-yl)-6,8,8-tripropyldesmosdumotin B
  参考文献：
  名称：

  Antitumor Agents. 284. New Desmosdumotin B Analogues with Bicyclic B-Ring as Cytotoxic and Antitubulin Agents

  摘要：

  We previously reported that the biological activity of analogues of desmosdumotin B (1) was dramatically changed depending on the B-ring system. A naphthalene B-ring analogue 3 exerted potent in vitro activity against a diverse panel of human tumor cell lines with GI(50) values of 0.8-2.1 mu M. In contrast, 1 analogues with a phenyl B-ring showed unique selective activity against P-glycoprotein (P-gp) over-expressing multidrug resistant cell line. We have now prepared and evaluated, 1 analogues with bicyclic or tricyclic aromatic B-ring systems as in vitro inhibitors of human cancer cell line proliferation. Among all synthesized derivatives, 21 with a benzo[b]thiophenyl B-ring was highly active, with GI(50) values of 0.06-0.16 mu M, and this activity was not influenced by overexpression of P-gp. Furthermore, 21 inhibited tubulin assembly in vitro with an IC(50) value of 2.0 mu M and colchicine binding by 7896 as well as cellular microtubule polymerization and spindle formation.

  DOI：

  10.1021/jm1011947
• 作为产物：
  描述：

  2,4,6-三羟基苯乙酮一水合物 在 sodium methylate 作用下， 以 甲醇 、 乙醚 、 乙酸乙酯 为溶剂， 反应 10.0h， 生成 2-acetyl-3-hydroxy-5-methoxy-4,4,6-tripropylcyclohexa-2,5-dienone
  参考文献：
  名称：

  Antitumor Agents 259. Design, Syntheses, and Structure−Activity Relationship Study of Desmosdumotin C Analogs

  摘要：

  Desmosdumotin C (1) and its analogs previously showed potent, selective in vitro anticancer activity. To explore structure-activity relationships of 1 and further increase potency and selectivity, 15 novel analogs (7-15 and 21-26) were synthesized and evaluated for cytotoxity against several human tumor cell lines, as well as inhibition of human endothelial (HUVEC) replication. 4-Bromo-3',3',5'-tripropyl analog 26 showed significant cytotoxity against A549, A431, 1A9, and HCT-8 with ED50 values of 1.0, 1.2, 0.9, and 1.3 mu g/mL, respectively. Compound 26 also strongly inhibited the growth of matched tumor cells, KB-VIN and its parent cell KB. Furthermore, analogs 13 and 21 were over 5-fold more potent against KB-VIN than KB. Bromination of ring-B and tripropyl functionalization of ring-A enhanced activity, while alkylation of ring-B promoted KB-VIN/KB selectivity. 2-Furyl analog 16 showed selective activity against HUVEC, suggesting that it may have potential as a new prototype for angiogenesis inhibition.

  DOI：

  10.1021/jm0702534

文献信息

• Antitumor Agents 260. New Desmosdumotin B Analogues with Improved In Vitro Anticancer Activity
  作者：Kyoko Nakagawa-Goto、Kenneth F. Bastow、Tzu-Hsuan Chen、Susan L. Morris-Natschke、Kuo-Hsiung Lee

  DOI：10.1021/jm701208v

  日期：2008.6.1

  Sixteen analogues (3-16, 33, and 48) of the unique flavonoid desmosdumotin B (1) were prepared and evaluated as in vitro inhibitors of the human KB cancer cell line and its MDR subclone, KB-VIN. 6,8,8-Triethyl analogues 10-13 showed enhanced KB-VIN selectivity. In particular, 4'-alkyl derivatives 11 (4'-Me) and 12 (4'-Et) showed significant ED50 values of 0.03 and 0.025 mu g/mL, respectively, against KB-VIN with selectivities of > 460- and 320-fold compared with that of KB. This report is the first to describe compounds showing such high activity against MDR cells versus non-MDR cells. The unique activity of 1-analogues is likely MDR-mediated because cotreatment with verapamil, a P-gp inhibitor, partially reversed the selective toxicity of both 1 and 10. Interestingly, only 1-analogues with a naphthalene B-ring (8 and 14) showed significant cytotoxic activity against KB; and other cancer cell lines. Thus, 1-analogues might be a new class of potent drug candidates, especially as 11 and 12 express direct selective action against tumors expressing MDR.
• Antitumor agents 283. Further elaboration of Desmosdumotin C analogs as potent antitumor agents: Activation of spindle assembly checkpoint as possible mode of action
  作者：Kyoko Nakagawa-Goto、Pei-Chi Wu、Kenneth F. Bastow、Shuenn-Chen Yang、Sung-Liang Yu、Hsuan-Yu Chen、Jau-Chen Lin、Masuo Goto、Susan L. Morris-Natschke、Pan-Chyr Yang、Kuo-Hsiung Lee

  DOI：10.1016/j.bmc.2011.01.001

  日期：2011.3

  In our ongoing study of the desmosdumotin C (1) series, twelve new analogues, 21-32, mainly with structural modifications in ring-A, were prepared and evaluated for in vitro antiproliferative activity against several human tumor cell lines. Among them, the 40-iodo-3,3,5-tripropyl-4-methoxy analogue (31) showed significant antiproliferative activity against multiple human tumor cell lines with ED50 values of 1.1-2.8 mu M. Elongation of the C-3 and C-5 carbon chains reduced activity relative to propyl substituted analogues; however, activity was still better than that of natural compound 1. Among analogues with various ether groups on C-4, compounds with methyl (2) and propyl (26) ethers inhibited cell growth of multiple tumor cells lines, while 28 with an isobutyl ether showed selective antiproliferative activity against lung cancer A549 cells (ED50 1.7 mu M). The gene expression profiles showed that 3 may modulate the spindle assembly checkpoint (SAC) and chromosome separation, and thus, arrest cells at the G2/M-phase. (C) 2011 Elsevier Ltd. All rights reserved.