2-acetyl-6-ethyl-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dienone | 946147-97-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯基酸
• 英文名称: 2-acetyl-6-ethyl-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dienone
• CAS: 946147-97-3
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: YSMNAQRGAATZHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74.6
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-acetyl-6-ethyl-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dienone 在 氢氧化钾 作用下， 以 甲醇 、 乙醚 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 4-ethyl-3-hydroxy-5-methoxy-6,6-dimethyl-2-[(E)-3-phenylprop-2-enoyl]cyclohexa-2,4-dien-1-one
  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
• 作为产物：
  描述：

  2-乙酰基-3,5-二羟基-4,4-二甲基-2,5-环己二烯-1-酮 、 碘乙烷 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以24%的产率得到2-acetyl-6-ethyl-3,5-dihydroxy-4,4-dimethylcyclohexa-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.