10β-(2-bromoethoxy)dihydroartemisinin

• 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: 10β-(2-bromoethoxy)dihydroartemisinin
• 英文别名: 12-β-(2-bromoethoxy)-dihydroartemisinin；12-α-O-(2-bromoethyl)dihydroartemisinin；2-(10β-dihydroartemisinoxy)ethylbromide；(1S,4S,5R,8S,9R,10S,12R,13R)-10-(2-bromoethoxy)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
• 化学式: C₁₇H₂₇BrO₅
• 分子量: 391.302
• InChiKey: JYETWHOZAFUUCQ-RRIGHJONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  10β-(2-bromoethoxy)dihydroartemisinin 在 水 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 乙醇 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  一类新型青蒿素衍生物、合成方法及其用途

  摘要：

  本发明公开了一类新型青蒿素衍生物、合成方法及其用途。该衍生物的结构如通式I所示，各取代基的定义如说明书和权利要求书所述。本发明的衍生物，能够作为抗凋亡蛋白抑制剂，对Bcl‑2具有较好的抑制作用。

  公开号：

  CN110143974B
• 作为产物：
  描述：

  artemisinin 在 甲醇 、 sodium tetrahydroborate 、 dodecatungstophosphoric acid hydrate 作用下， 以 甲醇 为溶剂， 反应 29.17h， 生成 10β-(2-bromoethoxy)dihydroartemisinin
  参考文献：
  名称：

  二氢青蒿素与γ-氨基丁酸的协同整合产生更潜在的抗抑郁药

  摘要：

  已经设计并合成了三种二氢青蒿素 (DHA) 与 β-氨基丙酸、γ-氨基丁酸和组胺的混合物。DHA 与 GABA 标记为5b的缀合物被证实是对抗 Cort 和 SNP 诱导的 PC12 细胞损伤的最有效候选物，EC 50值分别为 8.04 ± 0.35 和 9.38 ± 0.56 μM。5b被清楚地强调为 Akt、Bcl-2 和 Bax 蛋白质表达的良好调节剂，表明其具有对抗程序性细胞凋亡的功能。5b显着逆转了 Cort 诱导的过度钙内流和内部细胞器的释放。已证明能够表达增加水平的 β-微管蛋白 III 并上调 cAMP 反应元件结合蛋白 (CREB) 的磷酸化水平，从而导致细胞分化。它可以以适当的稳定性穿透血脑屏障（BBB）。总之，这些数据强烈支持5b是一种潜在的抗抑郁药。

  DOI：

  10.1016/j.bioorg.2021.104769

文献信息

• Synthesis of novel 1,2,3-triazole based artemisinin derivatives and their antiproliferative activity
  作者：Deepak Singh Kapkoti、Shilpi Singh、Suaib Luqman、Rajendra Singh Bhakuni

  DOI：10.1039/c7nj04271j

  日期：——

  molecules are non-toxic even at the highest tested concentration (100 μg mL−1). Some 3α-hydroxydeoxydihydroartemisinin-triazole derivatives (11a, 14a, 15a, 17a–22a) were also synthesized along with their peroxy counterparts. The antiproliferative activity results revealed that, except for compound 11a, all the compounds with peroxy functionality are more active than their 3α-hydroxydeoxy counterparts.

  设计了两个新的基于1,2,3-三唑的青蒿素衍生物系列，它们是通过铜（I）催化的叠氮化物炔烃环加成（CuAAC）反应合成的，并通过MTT分析研究了它们对多种人类癌细胞系的抗增殖活性。在系列1，化合物9，17，18，和22显示针对所有测试的细胞系中更好的抗增殖活性相比，双氢青蒿素（DHA，5）。化合物9和化合物17的活性最高，IC 50分别为4.06至36.65μM和7.16至28.21μM。化合物9化合物17对A431细胞系表现出有效的抗增殖活性，IC 50为4.06μM，化合物17对A549细胞系表现出有效的增殖活性，IC 50为7.16μM。在串联的2个中，化合物24，27和28显示出更好的活性比其它衍生物。活性化合物9和17在G2 / M期表现出显着（p <0.05）的细胞周期停滞以及皮肤和肺癌细胞的凋亡。这些分子显着（p<0.05）诱导受试细胞系中ROS的形成。此外，对人类红细胞的毒
• Design, Synthesis and Evaluation of the Antibacterial Enhancement Activities of Amino Dihydroartemisinin Derivatives
  作者：Chong Wu、Jian Liu、Xichun Pan、Wenying Xian、Bin Li、Wei Peng、Jingfang Wang、Dacheng Yang、Hong Zhou

  DOI：10.3390/molecules18066866

  日期：——

  Artemisinin (ART) and its derivatives artesunate (AS), dihydroartemisinin (DHA) are a group of drugs containing a sesquiterpene lactone used to treat malaria. Previously, AS was shown to not have antibacterial activity but to significantly increase the antibacterial activities of β-lactam antibiotics against E. coli. Herein, molecular docking experiments showed that ART, AS and DHA could dock into AcrB very well, especially DHA and AS; both DHA and AS had the same docking pose. The affinity between AS and AcrB seemed weaker than that of DHA, while the succinate tail of AS, which was like a “bug”, could extend in the binding pocket very well. Imitating the parent nucleus of DHA and the succinate tail of AS, twenty-one DHA derivatives 4a–u were designed and synthesized. Among them, seventeen were new compounds. The synergistic effects against E. coli AG100A/pET28a-AcrB showed among the new structures 4k, 4l, 4m, 4n, and 4r exhibited significant synergism with β-lactam antibiotics although they had no direct antibacterial activities themelves. The bacterial growth assay showed that only 4k in combination with ampicillin or cefuroxime could totally inhibit bacterial growth from 0 to 12 h, demonstrating that 4k had the best antibacterial enhancement effect. In conclusion, our results provided a new idea and several candidate compounds for antibacterial activity enhancers against multidrug resistant E. coli.

  青蒿素（ART）及其衍生物青蒿琥酯（AS）、双氢青蒿素（DHA）是一组含有倍半萜内酯的药物，用于治疗疟疾。以前的研究表明，青蒿琥酯没有抗菌活性，但能显著提高β-内酰胺类抗生素对大肠杆菌的抗菌活性。分子对接实验表明，ART、AS和DHA能很好地与AcrB对接，尤其是DHA和AS；DHA和AS具有相同的对接姿态。AS与AcrB的亲和力似乎弱于DHA，而AS的琥珀酸尾部就像一个 "虫子"，能很好地在结合口袋中延伸。模仿 DHA 的母核和 AS 的琥珀酸尾，设计并合成了 21 种 DHA 衍生物 4a-u。其中 17 个是新化合物。对大肠杆菌 AG100A/pET28a-AcrB 的协同作用表明，新结构中的 4k、4l、4m、4n 和 4r 虽然本身没有直接的抗菌活性，但与β-内酰胺类抗生素有显著的协同作用。细菌生长试验表明，只有 4k 与氨苄西林或头孢呋辛合用才能完全抑制细菌在 0 至 12 小时内的生长，这表明 4k 的抗菌增强效果最好。总之，我们的研究结果为抗耐多药大肠杆菌的抗菌活性增强剂提供了一种新的思路和几种候选化合物。
• Cannabidiol-dihydroartemisinin conjugates for ameliorating neuroinflammation with reduced cytotoxicity
  作者：Fanfan Wang、Ming Li、Cong Lin、Sha Jin、Hongyuan Li、Yuyuan Lu、Hengshan Wang、Hongshuang Wang、Xiaohui Wang

  DOI：10.1016/j.bmc.2021.116131

  日期：2021.6
• Design, synthesis, and biological evaluation of dihydroartemisinin–fluoroquinolone conjugates as a novel type of potential antitubercular agents
  作者：Fu-Wei Zhou、Huang-Shu Lei、Li Fan、Li Jiang、Jian Liu、Xin-Mei Peng、Xing-Ran Xu、Li Chen、Cheng-He Zhou、Yan-Ye Zou、Cai-Ping Liu、Zhi-Qin He、Da-Cheng Yang

  DOI：10.1016/j.bmcl.2014.03.010

  日期：2014.4

  Tuberculosis remains a global public health problem in recent years. To develop novel type of potential antitubercular agents, twelve novel dihydroartemisinin-fluoroquinolone (DHA-FQ) conjugates (three types of molecules) were gradually designed and conveniently synthesized. All the newly synthesized conjugates were well characterized and evaluated against different Mycobacterium tuberculosis strains in vitro. The screening results showed that five DHA-FQ conjugates were active toward M. tuberculosis H37Rv, and compound 3a exhibited the strongest inhibitory activity (MIC = 0.0625 mu g/mL), which was comparable to the positive control Moxifloxacin and even stronger than Ofloxacin. Conjugates 2a and 3a also displayed comparable activities against various clinically isolated sensitive and resistant M. tuberculosis strains (MIC = 0.125-16 mu g/mL) to Moxifloxacin. All target compounds possessed selective anti-M. tuberculosis ability. Preliminary structure-activity relationship demonstrated that short linker between DHA and FQ was favorable for strong antitubercular activity. This study provides a new clue for the development of novel antitubercular lead molecules. (c) 2014 Published by Elsevier Ltd.
• Synthesis, in vitro antimalarial and cytotoxicity of artemisinin-aminoquinoline hybrids
  作者：Marli C. Lombard、David D. N’Da、Jaco C. Breytenbach、Peter J. Smith、Carmen A. Lategan

  DOI：10.1016/j.bmcl.2011.01.103

  日期：2011.3

  Dihydroartemisinin (DHA) was coupled to different aminoquinoline moieties forming hybrids 9-14, which were then treated with oxalic acid to form oxalate salts (9a-14a). Compounds 9a, 10a, 12, 12a, and 14a showed comparable potency in vitro to that of chloroquine (CQ) against the chloroquine sensitive (CQS) strain, and were found to be more potent against the chloroquine resistant CQR strain. Hybrids 12 and its oxalate salt 12a were the most active against CQR strain, being 9- and 7-fold more active than CQ, respectively (17.12 nM; 20.76 nM vs 157.9 nM). An optimum chain length was identified having 2 or 3 Cs with or without an extra methylene substituent. (C) 2011 Elsevier Ltd. All rights reserved.