(R)-evodiamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (R)-evodiamine
• 英文别名: evodiamine；(1R)-21-methyl-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15,17,19-heptaen-14-one
• 化学式: C₁₉H₁₇N₃O
• 分子量: 303.363
• InChiKey: TXDUTHBFYKGSAH-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  39.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  吴茱萸碱 在 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-dimethyl-d₆-formamide 为溶剂， 反应 10.5h， 生成 (R)-evodiamine
  参考文献：
  名称：

  Quinazolinecarboline alkaloid evodiamine as scaffold for targeting topoisomerase I and sirtuins

  摘要：

  This paper reports the synthesis of a series of evodiamine derivatives. We assayed the ability to inhibit cell growth on three human tumour cell lines (H460, MCF-7 and HepG2) and we evaluated the capacity to interfere with the catalytic activity of topoisomerase I both by the relaxation assay and the occurrence of the cleavable complex. Moreover, whose effect on sirtuins 1, 2 and 3 was investigated. Finally, molecular docking analyses were performed in an attempt to rationalize the biological results. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.030

文献信息

• Effect of chirality and lipophilicity in the functional activity of evodiamine and its analogues at TRPV1 channels
  作者：Luciano De Petrocellis、Aniello Schiano Moriello、Gabriele Fontana、Alessandro Sacchetti、Daniele Passarella、Giovanni Appendino、Vincenzo Di Marzo

  DOI：10.1111/bph.12320

  日期：2014.5

  Background and PurposeEvodiamine, a racemic quinazolinocarboline alkaloid isolated from the traditional Chinese medicine Evodiae fructus, has been reported to act as an agonist of the transient receptor potential vanilloid type‐1 (TRPV1) cation channel both in vitro and in vivo. Evodiamine is structurally different from all known TRPV1 activators, and has significant clinical potential as a thermogenic agent. Nevertheless, the molecular bases for its actions are still poorly understood.Experimental ApproachTo investigate the structure‐activity relationships of evodiamine, the natural racemate was resolved, and a series of 23 synthetic analogues was prepared, using as the end point the intracellular Ca2+ elevation in HEK‐293 cells stably overexpressing either the human or the rat recombinant TRPV1.Key ResultsS‐(+) evodiamine was more efficacious and potent than R‐(−) evodiamine, and a new potent lead (Evo30) was identified, more potent than the reference TRPV1 agonist, capsaicin. In general, potency and efficacy correlated with the lipophilicity of the analogues. Like other TRPV1 agonists, several synthetic analogues could efficiently desensitize TRPV1 to activation by capsaicin.Conclusions and ImplicationsEvodiamine qualifies as structurally unique lead structure to develop new potent TRPV1 agonists/desensitizers.Linked ArticlesThis article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐10
• Quinazolinecarboline alkaloid evodiamine as scaffold for targeting topoisomerase I and sirtuins
  作者：Michael S. Christodoulou、Alessandro Sacchetti、Valentina Ronchetti、Stefania Caufin、Alessandra Silvani、Giordano Lesma、Gabriele Fontana、Fabrizio Minicone、Benedetta Riva、Micol Ventura、Maija Lahtela-Kakkonen、Elina Jarho、Valentina Zuco、Franco Zunino、Nadine Martinet、Federico Dapiaggi、Stefano Pieraccini、Maurizio Sironi、Lisa Dalla Via、Ornella Maria Gia、Daniele Passarella

  DOI：10.1016/j.bmc.2013.09.030

  日期：2013.11

  This paper reports the synthesis of a series of evodiamine derivatives. We assayed the ability to inhibit cell growth on three human tumour cell lines (H460, MCF-7 and HepG2) and we evaluated the capacity to interfere with the catalytic activity of topoisomerase I both by the relaxation assay and the occurrence of the cleavable complex. Moreover, whose effect on sirtuins 1, 2 and 3 was investigated. Finally, molecular docking analyses were performed in an attempt to rationalize the biological results. (C) 2013 Elsevier Ltd. All rights reserved.