1-acetoxy-9-benzoyloxy-8-trans-cinnamoyloxy-4,6-dihydroxy-dihydro-β-agarofuran | 1034159-66-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 1-acetoxy-9-benzoyloxy-8-trans-cinnamoyloxy-4,6-dihydroxy-dihydro-β-agarofuran
• 英文别名: [(1S,2S,5S,6S,7R,8S,9S,12R)-5-acetyloxy-2,12-dihydroxy-2,6,10,10-tetramethyl-8-[(E)-3-phenylprop-2-enoyl]oxy-11-oxatricyclo[7.2.1.01,6]dodecan-7-yl] benzoate
• CAS: 1034159-66-4
• 化学式: C₃₃H₃₈O₉
• 分子量: 578.659
• InChiKey: KAPQKCUDPVRZEX-ZGIPRAPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-acetoxy-9-benzoyloxy-8-trans-cinnamoyloxy-4,6-dihydroxy-dihydro-β-agarofuran 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 20.0 ℃ 、400.01 kPa 条件下， 反应 1.25h， 以95.7%的产率得到[(1S,2S,5S,6S,7R,8S,9S,12R)-5-acetyloxy-2,12-dihydroxy-2,6,10,10-tetramethyl-8-(3-phenylpropanoyloxy)-11-oxatricyclo[7.2.1.01,6]dodecan-7-yl] benzoate
  参考文献：
  名称：

  Optimization by Molecular Fine Tuning of Dihydro-β-agarofuran Sesquiterpenoids as Reversers of P-Glycoprotein-Mediated Multidrug Resistance

  摘要：

  P-glycoprotein (P-gp) plays a crucial role in the development of multidrug resistance (MDR), a major obstacle for successful chemotherapy in cancer. Herein, we report on the development of a natural-product-based library of 81 dihydro-fiagarofuran sesquiterpenes (2-82) by optimization of the lead compound 1. The compound library was evaluated for its ability to inhibit P-gp-mediated daunomycin efflux in MDR cells. Selected analogues were further analyzed for their P-gp inhibition constant, intrinsic toxicity, and potency to reverse daunomycin and vinblastine resistances. Analogues 6, 24, 28, 59, and 66 were identified as having higher potency than compound 1 and verapamil, a first-generation P-gp modulator. SAR analysis revealed the size of the aliphatic chains and presence of nitrogen atoms are important structural characteristics to modulate reversal activity. The present study highlights the potential of these analogues as modulators of P-gp mediated MDR in cancer cells.

  DOI：

  10.1021/acs.jmedchem.5b01429

文献信息

• Dihydro-β-agarofuran sesquiterpenes isolated from Celastrus vulcanicola as potential anti-Mycobacterium tuberculosis multidrug-resistant agents
  作者：David Torres-Romero、Ignacio A. Jiménez、Rosario Rojas、Robert H. Gilman、Matías López、Isabel L. Bazzocchi

  DOI：10.1016/j.bmc.2011.02.034

  日期：2011.4

  In the present study, we report four new dihydro-beta-agarofuran sesquiterpenes (1-4), which were isolated from the leaves of Celastrus vulcanicola, in addition to five derivatives (5-9). Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, X-ray studies, chemical correlations and biogenetic means. Compounds 1-9 and the previously reported sesquiterpenes 10-25 have been tested as potential antimycobacterial agents against sensitive and resistant Mycobacterium tuberculosis strains. 1 alpha-Acetoxy-6 beta,9 beta-dibenzoyloxy-dihydro-beta-agarofuran (20) exhibited antituberculosis activity against the MDR TB strain with a MIC value of 6.2 mu g/mL, comparable to or better than isoniazid or rifampin, two of the best first-line drugs commonly used in the treatment of TB. The structure-activity relationship is discussed. (C) 2011 Elsevier Ltd. All rights reserved.
• Optimization by Molecular Fine Tuning of Dihydro-β-agarofuran Sesquiterpenoids as Reversers of P-Glycoprotein-Mediated Multidrug Resistance
  作者：Oliver Callies、María P. Sánchez-Cañete、Francisco Gamarro、Ignacio A. Jiménez、Santiago Castanys、Isabel L. Bazzocchi

  DOI：10.1021/acs.jmedchem.5b01429

  日期：2016.3.10

  P-glycoprotein (P-gp) plays a crucial role in the development of multidrug resistance (MDR), a major obstacle for successful chemotherapy in cancer. Herein, we report on the development of a natural-product-based library of 81 dihydro-fiagarofuran sesquiterpenes (2-82) by optimization of the lead compound 1. The compound library was evaluated for its ability to inhibit P-gp-mediated daunomycin efflux in MDR cells. Selected analogues were further analyzed for their P-gp inhibition constant, intrinsic toxicity, and potency to reverse daunomycin and vinblastine resistances. Analogues 6, 24, 28, 59, and 66 were identified as having higher potency than compound 1 and verapamil, a first-generation P-gp modulator. SAR analysis revealed the size of the aliphatic chains and presence of nitrogen atoms are important structural characteristics to modulate reversal activity. The present study highlights the potential of these analogues as modulators of P-gp mediated MDR in cancer cells.