黄卡瓦胡椒素 C | 37308-75-1

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 中文名称: 黄卡瓦胡椒素 C
• 中文别名: 黄卡瓦胡椒素C
• 英文名称: flavokawain C
• 英文别名: flavokavain C；2',4-Dihydroxy-4',6'-dimethoxychalcone；(E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one
• CAS: 37308-75-1
• 化学式: C₁₇H₁₆O₅
• 分子量: 300.311
• InChiKey: UXUFMIJZNYXWDX-VMPITWQZSA-N

物化性质

• 熔点：
  179-182 °C
• 沸点：
  556.0±50.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：12.5 mg/mL（41.62 mM）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• WGK Germany：
  3

制备方法与用途

生物活性

Flavokawain C 是存在于卡瓦胡椒根中的天然查尔酮。研究显示，它对多种人类癌症细胞系具有细胞毒性，其中对 HCT 116 细胞的作用 IC50 值为 12.75 μM。

化学性质

Flavokawain C 是一种淡黄色粉末，可溶于甲醇、乙醇和 DMSO 等有机溶剂。它来源于胡椒科卡瓦胡椒（Piper methysticum Forst）的根茎。

用途

Flavokawain C 主要用于含量测定、鉴定以及药理实验等。

反应信息

• 作为反应物：
  描述：

  黄卡瓦胡椒素 C 以 甲醇 、 水 为溶剂， 生成 2-(4-羟基苯基)-5,7-二甲氧基-2,3-二氢-4H-苯并吡喃-4-酮
  参考文献：
  名称：

  Prenylflavonoid variation in Humulus lupulus: distribution and taxonomic significance of xanthogalenol and 4′-O-methylxanthohumol

  摘要：

  The resins produced by either lupulin or leaf glands of over 120 plants of Humulus lupulus and one plant of H. japonicus (Cannabinaceae) were analyzed for the presence of prenylated flavonoids. The H. lupulus taxa investigated were H. lupulus var. lupulus from Europe, H. lupulus var. cordifolius from Japan, and H. lupulus From North America. Fifty-two of the plants examined were cultivars of European, American, and Japanese origin, Twenty-two flavonoids were detected in the glandular exudates of. H. lupulus by HPLC-MS-MS. Xanthohumol (3'-prenyl-6'-O-methylchalconaringenin) was the principal prenylflavonoid in all H. lupulus plants and was accompanied by 11 structurally similar chalcones. Ten flavonoids were identified as the flavanone isomers of these chalcones. Three other prenylchalcones were isolated from H. lupulus cv. 'Galena', one of which was identified as 3'-prenyl-4'-O-methylchalconaringenin (named 'xanthogalenol'). The distribution of three 4'-O-methylchalcones, i.e, xanthogalenol, 4'-O-methylxanthohumol, and 4',6'-di-O-methylchalconaringenin, was found to be limited to wild American plants from the Missouri-Mississippi river basin, H. lupulus var. cordifolius, and most of their descendents, These 4'-O-methylchalcones were absent from cultivars of European origin; and from wild hops from Europe and southwestern USA, The flavonoid dichotomy (presence versus absence of 4'-O-methylchalcones) indicates that there are at least two evolutionary lineages within H. lupulus (European and Japanese-American). which is in agreement with morphological, molecular, and phytogeographical evidence. Leaf glands of H. japonicus from eastern Asia did not produce the N. lupulus prenylflavonoids. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0031-9422(00)00005-4
• 作为产物：
  描述：

  2’,4’-dimethoxy-6’-hydroxy-4-O-methoxymethylchalcone 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 0.25h， 以70%的产率得到黄卡瓦胡椒素 C
  参考文献：
  名称：

  Synthesis, Cytotoxicity, and Antioxidative Activity of Minor Prenylated Chalcones from Humulus lupulus

  摘要：

  The minor hop (Humulus lupulus) chalcones 3'-geranylchalconaringenin (3), 5'-prenylxanthohumol (4), flavokawin (5), xanthohumol H (8), xanthohumol C (9), and 1 '',2 ''-dihydroxanthohumol C (10) were synthesized. The non-natural chalcones 3'-geranyl-6'-O-methylchalconaringenin (2), 3'-methylflavokawin (6), and 2'-O-methyl-3'-prenylchalconar-. ingenin (7) were also synthesized. Cytotoxicity was investigated in HeLa cells, and these compounds all had IC50 values comparable to xanthohumol (8.2-19.2 mu M). The ORAC-fluorescein assay revealed potent antioxidative activity for 7 and 8 with 5.2 and 4.8 Trolox equivalents, respectively.

  DOI：

  10.1021/np800188b

文献信息

• Synthesis of Flavokawain Analogues and their Anti-neoplastic Effects on Drug-resistant Cancer Cells Through Hsp90 Inhibition
  作者：Young Ho Seo、Sun You Park

  DOI：10.5012/bkcs.2014.35.4.1154

  日期：2014.4.20

  Hsp90 is an ubiquitous molecular chaperone protein, which plays an important role in regulating maturation and stabilization of many oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 represents great promise as a therapeutic target of cancer. In this study, we synthesized flavokawain analogues and evaluated their biological activities against drug-resistant cancer cells. The study indicated that compound 1i impaired the growth of gefitinib-resistant non-small cell lung cancer (H1975), down-regulated the expression of Hsp90 client proteins including EGFR, Her2, Met, Akt and Cdk4, and upregulated the expression of Hsp70. The result strongly suggested that compound 1i inhibited the proliferation of cancer cells through Hsp90 inhibition. Overall, compound 1i could serve as a potential lead compound to overcome the drug resistance in cancer chemotherapy.

  Hsp90是一种普遍存在的分子伴侣蛋白，在调节多种致癌蛋白的成熟和稳定中起着重要作用。由于其同时禁用多个信号通路的潜力，Hsp90作为癌症的治疗靶点具有巨大前景。在本研究中，我们合成了黄卡瓦醇类似物，并评估了它们对耐药癌细胞的生物活性。研究表明，化合物1i损害了吉非替尼耐药的非小细胞肺癌（H1975）的生长，下调了包括EGFR、Her2、Met、Akt和Cdk4在内的Hsp90客户蛋白的表达，并上调了Hsp70的表达。结果强烈表明，化合物1i通过抑制Hsp90抑制了癌细胞的增殖。总的来说，化合物1i有可能作为一种潜在的先导化合物，克服癌症化疗中的药物耐药性。
• Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation
  作者：Youzhe Yang、Zhe Wei、Alexander Tobias Teichmann、Frank Heinrich Wieland、Amu Wang、Xiangui Lei、Yue Zhu、Jinxiang Yin、Tiantian Fan、Li Zhou、Chao Wang、Lijuan Chen

  DOI：10.1016/j.ejmech.2020.112216

  日期：2020.5

  at 10 μM (IC50 = 6.4 μM) with the lowest cytotoxicity (IC50 > 80 μM) among the tested compounds. Besides, western blot analysis indicated that compound 53 was a potent down-regulator of inducible nitric oxide synthase (iNOS) protein. Docking study revealed that compound 53 also can dock into the active site of iNOS. Furthermore, at the dose of 10 mg/kg/day, compound 53 could both significantly suppress

  炎症是对刺激的复杂生物学反应。活化的巨噬细胞诱导过度释放促炎性细胞因子，而内源性自由基一氧化氮（NO）等介体在多种炎性疾病的进展中起重要作用。天然和合成查耳酮都具有广泛的生物活性。在这项工作中，基于生物活性卡瓦尔查耳酮，设计，合成了39个查耳酮和3种相关化合物，包括几种新化合物，并评估了它们对RAW 264.7细胞中NO产生的抑制作用。新型化合物（E）-1-（2'-羟基-4'，6'-二甲氧基苯基）-3-（3-甲氧基-4-（3-吗啉代丙氧基）苯基）丙-2-烯-1-酮（53）对10μM（IC的NO产生）表现出更好的抑制活性（84.0％）50  = 6.4μM）的细胞毒性（IC 50  > 80μM）在测试化合物中最低。此外，蛋白质印迹分析表明化合物53是诱导型一氧化氮合酶（iNOS）蛋白的有效下调剂。对接研究表明，化合物53也可以对接iNOS的活性位点。此外，在剂量为10 mg / kg /
• Design, Synthesis and Biological Evaluation of Dimethyl Cardamonin (DMC) Derivatives as P-glycoprotein-mediated Multidrug Resistance Reversal Agents
  作者：Ximeng Shi、Yuyu Zhao、Licheng Zhou、Huanhuan Yin、Jianwen Liu、Lei Ma

  DOI：10.2174/1570180817999200531162015

  日期：2020.10.12

  Background: P-glycoprotein (P-gp) has been regarded as an important factor in the multidrug resistance (MDR) of tumor cells within the last decade, which can be solved by inhibiting Pgp to reverse MDR. Thus, it is an effective strategy to develop inhibitor of P-gp. Objective: In this study, the synthesis of a series of derivatives had been carried out by bioisosterism design on the basis of Dimethyl Cardamonin

  背景：过去十年来，P-糖蛋白（P-gp）被认为是肿瘤细胞多药耐药性（MDR）的重要因素，可以通过抑制Pgp逆转MDR来解决。因此，开发P-gp抑制剂是一种有效的策略。 目的：本研究在二甲基小豆蔻苷（DMC）的基础上，通过生物等位线设计进行了一系列衍生物的合成。随后，我们评估了它们作为潜在的P-糖蛋白（P-gp）介导的多药耐药性（MDR）药物的逆转活性。 方法：在40％KOH存在下，通过Claisen-Schmidt反应，由苯乙酮和相应的苯甲醛合成二甲基豆蔻苷衍生物。用MTT评估它们的体外细胞毒性和逆转活性。此外，通过阿霉素（DOX）积累，蛋白质印迹和伤口愈合分析对化合物B4进行了深入评估。 结果与讨论：结果表明，化合物B2，B4和B6具有MDR反向剂的效力，而固有的细胞毒性很小。同时，这些化合物还显示出抑制MCF-7和MCF-7 / DOX细胞迁移的能力。此外，选择了最多的化合物B4进行进一步的研究，它促进了DOX在MCF-7
• Insect Antifeedant Flavonoids from <i>Gnaphalium</i> <i>a</i><i>ffine</i> D. Don
  作者：Masanori Morimoto、Sumiko Kumeda、Koichiro Komai

  DOI：10.1021/jf990282q

  日期：2000.5.1

  The antifeedant flavonoids, 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (1), 5-hydroxy-3,6,7,8-tetramethoxyflavone (2), 5,6-dihydroxy-3, 7-dimethoxyflavone (3), and 4,4',6'-trihydroxy-2'-methoxychalcone (4), have been isolated from cudweed Gnaphalium affine D. Don (Compositae). Four natural flavonoids showed insect antifeedant activity against the common cutworm (Spodoptera litura F.). These flavonoids

  拒食类黄酮，5-羟基-3,6,7,8,4'-五甲氧基黄酮（1），5-羟基-3,6,7,8-四甲氧基黄酮（2），5,6-二羟基-3、7 -二甲氧基黄酮（3）和4,4'，6'-三羟基-2'-甲氧基查耳酮（4​​）已从商陆天牛仿制药D. Don（Compositae）中分离出来。四种天然类黄酮对普通地老虎（Spodoptera litura F.）具有昆虫拒食活性。通过HPLC分析在植物中少量检出了这些类黄酮，但这些天然化合物对普通地老虎具有很强的拒食活性。另一方面，在植物中大量检出了4种，但该化合物仅具有轻微的活性。因此，这些天然化合物与羊毛状植物表面一起被认为是植物对植物吞噬昆虫的防御系统之一。
• Flavokawains B and C, melanogenesis inhibitors, isolated from the root of Piper methysticum and synthesis of analogs
  作者：Hye-Jin Jeong、Chang Seok Lee、Janggyoo Choi、Yong Deog Hong、Song Seok Shin、Jun Seong Park、John Hwan Lee、Seokyong Lee、Kee Dong Yoon、Jaeyoung Ko

  DOI：10.1016/j.bmcl.2014.12.082

  日期：2015.2

  of Piper methysticum was found to inhibit melanogenesis in MSH-activated B16 melanoma cells. Flavokawains B and C were isolated from this extract based on their anti-melanogenesis activity and found to inhibit melanogenesis with IC50 values of 7.7 μM and 6.9 μM, respectively. Flavokawain analogs were synthesized through a Claisen–Schmidt condensation of their corresponding acetophenones and benzaldehydes

  发现胡椒的根的乙醇提取物抑制了MSH激活的B16黑色素瘤细胞中的黑色素生成。基于它们的抗黑素生成活性，从该提取物中分离出黄酮类固醇B和C，发现抑制黑素生成的IC 50值分别为7.7μM和6.9μM 。Flavokawain类似物是通过其相应的苯乙酮和苯甲醛的Claisen-Schmidt缩合反应合成的，并根据其酪氨酸酶抑制和抗黑色素生成活性进行了评估。在使用MSH激活的B16黑色素瘤细胞的黑色素生成抑制试验中，化合物1b最有效，IC 50值为2.3μM。