6,8,8-triethyl-2'-methyl desmosdumotin B | 1032423-26-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 6,8,8-triethyl-2'-methyl desmosdumotin B
• 英文别名: 6,8,8-Triethyl-2-methyl desmosdumotin B；6,8,8-triethyl-5-hydroxy-2-(2-methylphenyl)chromene-4,7-dione
• CAS: 1032423-26-9
• 化学式: C₂₂H₂₄O₄
• 分子量: 352.43
• InChiKey: IIZZOIPGGTUNCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 硫酸 、 碘 、 二甲基亚砜 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以66%的产率得到6,8,8-triethyl-2'-methyl desmosdumotin B
  参考文献：
  名称：

  Antitumor Agents 260. New Desmosdumotin B Analogues with Improved In Vitro Anticancer Activity

  摘要：

  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.

  DOI：

  10.1021/jm701208v

文献信息

• Antitumor Agents. 280. Multidrug Resistance-Selective Desmosdumotin B Analogues
  作者：Kyoko Nakagawa-Goto、Po-Cheng Chang、Chin-Yu Lai、Hsin-Yi Hung、Tzu-Hsuan Chen、Pei-Chi Wu、Hao Zhu、Alexander Sedykh、Kenneth F. Bastow、Kuo-Hsiung Lee

  DOI：10.1021/jm100846r

  日期：2010.9.23

  6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR selectivity. Three new disubstituted analogues, 35, 37, and 49, also had high collateral sensitivity (CS) indices of 273, 250, and 100, respectively. Furthermore, 2-4 also displayed MDR selectivity in an MDR hepatoma-cell system. While 2-4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively.