dihydrocurcumin | 76474-56-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: dihydrocurcumin
• 英文别名: DHC；(1E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-ene-3,5-dione；(E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-ene-3,5-dione
• CAS: 76474-56-1
• 化学式: C₂₁H₂₂O₆
• 分子量: 370.402
• InChiKey: MUYJSOCNDLUHPJ-XVNBXDOJSA-N

物化性质

• 熔点：
  179-180℃
• 沸点：
  616.3±55.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

Dihydrocurcumin 是姜黄素的主要代谢物，能够减少脂质堆积和氧化应激。它可以通过调节 SREBP-1C、PNPLA3 和 PPARα 的 mRNA 和蛋白水平，增加 pAKT 和 PI3K 的蛋白表达量，并通过 Nrf2 信号通路降低细胞内的 NO 和 ROS 含量。

化学性质

Dihydrocurcumin 是一种橙黄色粉末，可溶于甲醇、乙醇和 DMSO 等有机溶剂。它来源于姜黄。

用途

二氢姜黄素具有抗菌、消炎、抗肿瘤、抗氧化以及降血脂等多种作用。

反应信息

• 作为反应物：
  描述：

  dihydrocurcumin 生成 六氢姜黄素
  参考文献：
  名称：

  UEHARA, SHIN-ICHI;YASUDA, ICHIRO;AKIYAMA, KAZUYUKI;MORITA, HIROSHI;TAKEYA+, CHEM. AND PHARM. BULL., 35,(1987) N 8, 3298-3304

  摘要：

  DOI：
• 作为产物：
  描述：

  3-(4-羟基-3-甲氧基苯基)丙酸 在 盐酸 、 氢氧化钾 、 氯化亚砜 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 sodium iodide 作用下， 反应 23.0h， 生成 dihydrocurcumin
  参考文献：
  名称：

  Krishnamurty, H. G.; Ghosh, Sanjukta, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1986, vol. 25, p. 411 - 412

  摘要：

  DOI：

文献信息

• Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism
  作者：Azam Hassaninasab、Yoshiteru Hashimoto、Kaori Tomita-Yokotani、Michihiko Kobayashi

  DOI：10.1073/pnas.1016217108

  日期：2011.4.19

  Polyphenol curcumin, a yellow pigment, derived from the rhizomes of a plant ( Curcuma longa Linn) is a natural antioxidant exhibiting a variety of pharmacological activities and therapeutic properties. It has long been used as a traditional medicine and as a preservative and coloring agent in foods. Here, curcumin-converting microorganisms were isolated from human feces, the one exhibiting the highest activity being identified as Escherichia coli . We are thus unique in discovering that E. coli was able to act on curcumin. The curcumin-converting enzyme was purified from E. coli and characterized. The native enzyme had a molecular mass of about 82 kDa and consisted of two identical subunits. The enzyme has a narrow substrate spectrum, preferentially acting on curcumin. The microbial metabolism of curcumin by the purified enzyme was found to comprise a two-step reduction, curcumin being converted NADPH-dependently into an intermediate product, dihydrocurcumin, and then the end product, tetrahydrocurcumin. We named this enzyme “NADPH-dependent curcumin/dihydrocurcumin reductase” (CurA). The gene ( curA ) encoding this enzyme was also identified. A homology search with the BLAST program revealed that a unique enzyme involved in curcumin metabolism belongs to the medium-chain dehydrogenase/reductase superfamily.

  多酚姜黄素是一种来源于植物根茎（姜黄）的黄色色素，是一种天然抗氧化剂，展现出多种药理活性和治疗特性。长期以来，它一直被用作传统药物，以及食品的防腐剂和着色剂。在这里，从人类粪便中分离出了转化姜黄素的微生物，其中表现出最高活性的被鉴定为大肠杆菌。因此，我们发现大肠杆菌能够作用于姜黄素是独特的。从大肠杆菌中纯化并表征了转化姜黄素的酶。原生酶的分子量约为82 kDa，由两个相同的亚基组成。该酶具有狭窄的底物谱，优先作用于姜黄素。通过纯化酶对姜黄素的微生物代谢发现，包括一个两步还原过程，姜黄素首先以NADPH为辅助转化为一个中间产物，二氢姜黄素，然后形成最终产物四氢姜黄素。我们将这种酶命名为“NADPH依赖的姜黄素/二氢姜黄素还原酶”（CurA）。还鉴定了编码这种酶的基因（curA）。通过BLAST程序进行同源搜索，发现参与姜黄素代谢的独特酶属于中链脱氢酶/还原酶超家族。
• Isoxazole analogs of curcuminoids with highly potent multidrug-resistant antimycobacterial activity
  作者：Chatchawan Changtam、Poonpilas Hongmanee、Apichart Suksamrarn

  DOI：10.1016/j.ejmech.2010.07.003

  日期：2010.10

  bisdemethoxycurcumin (3), the curcuminoid constituents of the medicinal plant Curcuma longa L., have been structurally modified to 55 analogs and antimycobacterial activity against Mycobacterium tuberculosis has been evaluated. Among the highly active curcuminoids, the isoxazole analogs are the most active group, with mono-O-methylcurcumin isoxazole (53) being the most active compound (MIC 0.09 μg/mL). It was

  姜黄素（1），去甲氧基姜黄素（2）和双去甲氧基姜黄素（3）（药用植物姜黄的姜黄素成分）已在结构上修饰为55个类似物，并已评估了其对结核分枝杆菌的抗分枝杆菌活性。在高活性姜黄素类化合物中，异恶唑类似物是活性最高的基团，单-O-甲基姜黄素异恶唑（53）是活性最高的化合物（MIC 0.09μg/ mL）。它的活性比母体化合物姜黄素（1）高1131倍，分别比标准药物卡那霉素和异烟肼高18倍和2倍。化合物53还显示出对耐多药结核分枝杆菌临床分离株的高活性，MIC值为0.195–3.125μg/ mL。姜黄素类似物表现出抗分枝杆菌活性的结构要求是在异戊基环上存在一个异恶唑环和两个不饱和键。紧密连接于异恶唑环的氮官能团的芳环上合适的对烷氧基的存在和另一个芳环上的游离对羟基的存在增强了生物活性。
• Uehara, Shin-ichi; Yasuda, Ichiro; Akiyama, Kazuyuki, Chemical and pharmaceutical bulletin, 1987, vol. 35, # 8, p. 3298 - 3304
  作者：Uehara, Shin-ichi、Yasuda, Ichiro、Akiyama, Kazuyuki、Morita, Hiroshi、Takeya, Koichi、Itokawa, Hideji

  DOI：——

  日期：——
• Microbial transformation of curcumin by<i>Rhizopus chinensis</i>
  作者：Xing Zhang、Min Ye、Rui Li、Jun Yin、De-An Guo

  DOI：10.3109/10242422.2010.532870

  日期：2010.12

  Curcumin (1) is a potent antioxidant and antitumor natural product. In spite of its efficacy and safety, its clinical use is hindered mainly by poor water solubility and bioavailability. Structural modification to introduce hydrophilic functions is a promising approach to resolve this problem. In the present study we first found that curcumin could be efficiently converted into glucosides by filamentous fungi including Rhizopus chinensis IFFI 03043, Absidia coerulea AS 3.3389 and Cunninghamella elegans AS 3.1207. Curcumin 4'-O-beta-D-glucoside (2), together with hexahydrocurcumin (3), was isolated from a preparative-scale biotransformation with R. chinensis IFFI 03043 and characterized fully by NMR and MS. A time-course study revealed that curcumin could be efficiently converted into curcumin 4'-O-beta-D-glucoside within 8 h when administered at 0.05 mmol L-1 and the productivity was 57%. Additionally, the biotransformation products of curcumin by different fungal strains were analyzed by LC/MS. At least 15 metabolites were detected, and the predominant biotransformation reaction was glucosylation. This study provides a simple, efficient and less expensive approach for the preparation of curcumin glucosides. The introduction of the glucosyl function might be able to enhance the bioavailability of curcumin.
• Structural and Biochemical Characterization of the Curcumin-Reducing Activity of CurA from <i>Vibrio vulnificus</i>
  作者：Soo-Bong Park、Da-Woon Bae、Nina Abigail B. Clavio、Lei Zhao、Chang-Sook Jeong、Bo Mee Choi、Stephani Joy Y. Macalino、Hee-Jeong Cha、Jin-Byung Park、Jun Hyuck Lee、Sang-Jip Nam、Sun Choi、Min-Kyu Kim、Sun-Shin Cha

  DOI：10.1021/acs.jafc.8b03647

  日期：2018.10.10

  Curcumin is a yellow-colored ingredient in dietary spice turmeric (Curcuma longa Linn). This nontoxic polyphenol has antitumor, anti-inflammatory, apoptotic, and antioxidant activities. The ingested curcumin is reduced to multihydrated forms with more potent therapeutic potentials by the curcumin reductase (CurA) from commensal Escherichia coli. In this study, we demonstrated that Vibrio vulnificus CurA (VvCurA) with 87% sequence similarity to the E. coli CurA exhibits the curcumin-reducing activity through spectrophotometric detection of NADPH oxidation and high performance liquid chromatographic analysis of curcumin consumption and product generation. Afterward, we determined the crystal structures of VvCurA and the VvCurA/NADPH complex, and made the in silico model of the VvCurA/NADPH/curcumin ternary complex through induced fit docking. Based on structural information, active site residues that play critical roles in catalysis have been identified and characterized by mutational and kinetic studies, leading us to propose the reaction mechanism of CurA.