13-(2-ethoxy-2-oxoethyl)-9,10-dimethoxy-5,6-dihydrobenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium bromide

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: 13-(2-ethoxy-2-oxoethyl)-9,10-dimethoxy-5,6-dihydrobenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium bromide
• 英文别名: Ethyl 2-(16,17-dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaen-21-yl)acetate;bromide
• 化学式: Br*C₂₄H₂₄NO₆
• 分子量: 502.362
• InChiKey: BVXRXIRQRUAJKD-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.21
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  13-(2-ethoxy-2-oxoethyl)-9,10-dimethoxy-5,6-dihydrobenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium bromide 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 10.0h， 以94%的产率得到2-(16,17-Dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaen-21-yl)acetic acid;chloride
  参考文献：
  名称：

  <p>13-[CH2CO-Cys-(Bzl)-OBzl]-Berberine: Exploring The Correlation Of Anti-Tumor Efficacy With ROS And Apoptosis Protein</p>

  摘要：

  Background: The discovery of novel derivative of berberine (BBR) having higher antitumor activity in vivo is of clinical importance. In this profile, 13-[CH2CO-Cys-(Bzl)-OBzl]-berberine (13-Cys-BBR) was prepared for related assays.Purpose: The object of preparation and evaluation is to show the advantages of 13-Cys-BBR over BBR in both in vitro and in vivo anti-tumor actions, furthermore to correlate the proliferation of cancer cells with ROS formation and anti-apoptosis protein (XIAP) expression inside cancer cells.Methods: Transwell chamber was used to simulate the intestinal and cell wall for bioavailability evaluation; MTT assay was used to evaluate the in vitro anti-proliferation activity; fluorescein isothiocyanate content was used to represent ROS level in HCT-8 cells; Western blot assay was used to quantify the expression of XIAP, caspase-3, and poly ADP-ribose polymerase in HCT-8 cells; and 5180 mouse model was used to evaluate the in vivo antitumor activity.Results: In vitro the IC50 values (similar to 15-40 mu M) of 13-Cys-BBR against the proliferation of eight cancer cell lines were significantly lower than those of BBR (similar to 25-140 mu M); the content of ROS formed inside HCT-8 cells treated by 13-Cys-BBR was similar to 3.44-folds higher than that inside HCT-8 cells treated by BBR; the expression of XIAP in HCT-8 cells treated by 13-Cys-BBR was similar to 1.21-folds lower than that in HCT-8 cells treated by BBR; the tumor weight of 5180 mice orally treated by 2 mu mol/kg/day of 13-Cys-BBR (similar to 1.5 g) was significantly lower than that of 5180 mice orally treated by 2 mu mol/kg/day of BBR (similar to 2.5 g); and the active pocket of XIAP was more suitable for 13-Cys-BBR than for BBR.Conclusion: The anti-tumor action correlates with ROS and apoptosis protein, which suggests 13-Cys-BBR is a promising candidate for preclinical study.

  DOI：

  10.2147/ott.s231035
• 作为产物：
  描述：

  盐酸小檗碱 在 sodium iodide 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 13-(2-ethoxy-2-oxoethyl)-9,10-dimethoxy-5,6-dihydrobenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium bromide
  参考文献：
  名称：

  13位小Ber碱衍生物的合成和抗菌活性的评估。

  摘要：

  已知天然植物分子小ber碱的生物活性受结构修饰的影响，主要在9和/或13位。合成了一系列新的13位取代的小ber碱衍生物，并使用多种微生物进行了抗微生物活性评估。与人类疾病有关。与原始分子小ber碱相反，在对分枝杆菌，白色念珠菌和革兰氏阳性细菌的微生物敏感性测试中，发现了几种衍生物具有较强的活性，包括幼稚或耐药的蜡状芽孢杆菌，金黄色葡萄球菌和化脓性链球菌最小抑菌浓度（MIC）为3.12至6.25 µM。在所测试的各种革兰氏阴性菌株，黄连的衍生物只发现活性上幽门螺杆菌和弧菌溶藻弧菌（MIC值为1.5–3.12 µM）。对人细胞进行的细胞毒性试验表明，抗菌小碱衍生物引起的毒性低，从而产生了良好的治疗指数值。此外，一种机械方法证明，与引起膜透化，DNA断裂或与FtsZ蛋白相互作用的已知小already碱衍生物相反，本研究中所述的活性衍生物通过抑制肽聚糖或RNA的合成起作用。总体而言，这项研究表明

  DOI：

  10.3390/antibiotics9070381

文献信息

• The synthesis and antistaphylococcal activity of 9, 13-disubstituted berberine derivatives
  作者：Jing Wang、Teng Yang、Huang Chen、Yun-Nan Xu、Li-Fang Yu、Ting Liu、Jie Tang、Zhengfang Yi、Cai-Guang Yang、Wei Xue、Fan Yang

  DOI：10.1016/j.ejmech.2017.01.012

  日期：2017.2

  antibacterial activities against Staphylococcus aureus, including Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). Compound 20 shows the most potent activity against the growth of Newman strain, with a MIC value of 0.78 μg/mL, which is comparable with the positive control vancomycin. In addition, compound 20, 21, and 33 are highly antistaphylococcal active against

  合成了一系列新颖的9、13-双取代的小ber碱衍生物，并评估了其对金黄色葡萄球菌的抗菌活性，包括纽曼菌株和耐多药菌株（NRS-1，NRS-70，NRS-100，NRS-108和NRS-271）。化合物20对纽曼菌株的生长表现出最强的活性，MIC值为0.78μg/ mL，与阳性对照万古霉素相当。另外，化合物20，21和33是高度antistaphylococcal活性对耐多药的五种菌株的金黄色葡萄球菌，MIC值为0.78–1.56μg/ mL。值得注意的是，这些抗菌活性化合物在MIC浓度下对人成纤维细胞（HAF）细胞的活力没有明显的毒性。
• 8-Allyldihydroberberine as an Alternative Precursor for the Synthesis of 13-Substituted Berberine Derivatives
  作者：John B. Bremner、Siritron Samosorn

  DOI：10.1071/ch03054

  日期：——

  An alternative route to 13-substituted derivatives of the biologically active alkaloid berberine has been developed based on the key synthetic precursor, 8-allyldihydroberberine.

  在关键合成前体 8-烯丙基二氢小檗碱的基础上，开发出了生物活性生物碱小檗碱 13-取代衍生物的替代途径。
• Synthesis and Evaluation of the Antibacterial Activities of 13-Substituted Berberine Derivatives
  作者：Hamza Olleik、Taher Yacoub、Laurent Hoffer、Senankpon Martial Gnansounou、Kehna Benhaiem-Henry、Cendrine Nicoletti、Malika Mekhalfi、Valérie Pique、Josette Perrier、Akram Hijazi、Elias Baydoun、Josette Raymond、Philippe Piccerelle、Marc Maresca、Maxime Robin

  DOI：10.3390/antibiotics9070381

  日期：——

  berberine’s derivatives were only found active on Helicobacter pylori and Vibrio alginolyticus (MIC values of 1.5–3.12 µM). Cytotoxicity assays performed on human cells showed that the antimicrobial berberine derivatives caused low toxicity resulting in good therapeutic index values. In addition, a mechanistic approach demonstrated that, contrarily to already known berberine derivatives causing either

  已知天然植物分子小ber碱的生物活性受结构修饰的影响，主要在9和/或13位。合成了一系列新的13位取代的小ber碱衍生物，并使用多种微生物进行了抗微生物活性评估。与人类疾病有关。与原始分子小ber碱相反，在对分枝杆菌，白色念珠菌和革兰氏阳性细菌的微生物敏感性测试中，发现了几种衍生物具有较强的活性，包括幼稚或耐药的蜡状芽孢杆菌，金黄色葡萄球菌和化脓性链球菌最小抑菌浓度（MIC）为3.12至6.25 µM。在所测试的各种革兰氏阴性菌株，黄连的衍生物只发现活性上幽门螺杆菌和弧菌溶藻弧菌（MIC值为1.5–3.12 µM）。对人细胞进行的细胞毒性试验表明，抗菌小碱衍生物引起的毒性低，从而产生了良好的治疗指数值。此外，一种机械方法证明，与引起膜透化，DNA断裂或与FtsZ蛋白相互作用的已知小already碱衍生物相反，本研究中所述的活性衍生物通过抑制肽聚糖或RNA的合成起作用。总体而言，这项研究表明
• &lt;p&gt;13-[CH2CO-Cys-(Bzl)-OBzl]-Berberine: Exploring The Correlation Of Anti-Tumor Efficacy With ROS And Apoptosis Protein&lt;/p&gt;
  作者：Guanyu Li、Yi Ren、Xiaoyi Zhang、Shurui Zhao、Yaonan Wang、Jianhui Wu、Shiqi Peng、Ming Zhao

  DOI：10.2147/ott.s231035

  日期：——

  Background: The discovery of novel derivative of berberine (BBR) having higher antitumor activity in vivo is of clinical importance. In this profile, 13-[CH2CO-Cys-(Bzl)-OBzl]-berberine (13-Cys-BBR) was prepared for related assays.Purpose: The object of preparation and evaluation is to show the advantages of 13-Cys-BBR over BBR in both in vitro and in vivo anti-tumor actions, furthermore to correlate the proliferation of cancer cells with ROS formation and anti-apoptosis protein (XIAP) expression inside cancer cells.Methods: Transwell chamber was used to simulate the intestinal and cell wall for bioavailability evaluation; MTT assay was used to evaluate the in vitro anti-proliferation activity; fluorescein isothiocyanate content was used to represent ROS level in HCT-8 cells; Western blot assay was used to quantify the expression of XIAP, caspase-3, and poly ADP-ribose polymerase in HCT-8 cells; and 5180 mouse model was used to evaluate the in vivo antitumor activity.Results: In vitro the IC50 values (similar to 15-40 mu M) of 13-Cys-BBR against the proliferation of eight cancer cell lines were significantly lower than those of BBR (similar to 25-140 mu M); the content of ROS formed inside HCT-8 cells treated by 13-Cys-BBR was similar to 3.44-folds higher than that inside HCT-8 cells treated by BBR; the expression of XIAP in HCT-8 cells treated by 13-Cys-BBR was similar to 1.21-folds lower than that in HCT-8 cells treated by BBR; the tumor weight of 5180 mice orally treated by 2 mu mol/kg/day of 13-Cys-BBR (similar to 1.5 g) was significantly lower than that of 5180 mice orally treated by 2 mu mol/kg/day of BBR (similar to 2.5 g); and the active pocket of XIAP was more suitable for 13-Cys-BBR than for BBR.Conclusion: The anti-tumor action correlates with ROS and apoptosis protein, which suggests 13-Cys-BBR is a promising candidate for preclinical study.