5,6-didehydro-8,8-diethyl-13-oxodihydroberberine chloride | 1309576-27-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 5,6-didehydro-8,8-diethyl-13-oxodihydroberberine chloride
• 英文别名: 14,14-Diethyl-16,17-dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,11,15(20),16,18-octaen-21-one;chloride
• CAS: 1309576-27-9
• 化学式: C₂₄H₂₄NO₅*Cl
• 分子量: 441.911
• InChiKey: VVMXKNBRVWGFSG-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.99
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  小檗碱 在 sodium hydroxide 、 三氯氧磷 作用下， 反应 12.0h， 生成 5,6-didehydro-8,8-diethyl-13-oxodihydroberberine chloride
  参考文献：
  名称：

  Potent antiprotozoal activity of a novel semi-synthetic berberine derivative

  摘要：

  Treatment of diseases such as African sleeping sickness and leishmaniasis often depends on relatively expensive or toxic drugs, and resistance to current chemotherapeutics is an issue in treating these diseases and malaria. In this study, a new semi-synthetic berberine analogue, 5,6-didehydro-8, 8-diethyl-13-oxodihydroberberine chloride (1), showed nanomolar level potency against in vitro models of leishmaniasis, malaria, and trypanosomiasis as well as activity in an in vivo visceral leishmaniasis model. Since the synthetic starting material, berberine hemisulfate, is inexpensive, 8,8-dialkyl-substituted analogues of berberine may lead to a new class of affordable antiprotozoal compounds. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2011.01.101

文献信息

• 8,8-Dialkyldihydroberberines with Potent Antiprotozoal Activity
  作者：Molla Endeshaw、Xiaohua Zhu、Shanshan He、Trupti Pandharkar、Emily Cason、Kiran V. Mahasenan、Hitesh Agarwal、Chenglong Li、Manoj Munde、W. David Wilson、Mark Bahar、Raymond W. Doskotch、A. Douglas Kinghorn、Marcel Kaiser、Reto Brun、Mark E. Drew、Karl A. Werbovetz

  DOI：10.1021/np300638f

  日期：2013.3.22

  Semisynthetic 8,8-dialkyldihydroberberines (8,8-DDBs) were found to possess mid- to low-nanomolar potency against Plasmodium falciparum blood-stage parasites, Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei bloodstream forms. For example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50 values of 77, 100, and 5.3 nM against these three parasites, respectively. In turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-DDBs, were much less potent against these parasites in vitro. While the natural product berberine is a weak DNA binder, the 8,8-DDBs displayed no affinity for DNA, as assessed by changes in the melting temperature of poly(dA.dT) DNA. Selected 8,8-DDBs showed efficacy in mouse models of visceral leishmaniasis and African trypanosomiasis, with 8,8-dimethyldihydroberberine chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c mice when given at an intraperitoneal dose of 10 mg/kg/day for five days. The 8,8-DDBs may thus serve as leads for discovering new antimalarial, antileishmanial, and antitrypanosomal drug candidates.
• Potent antiprotozoal activity of a novel semi-synthetic berberine derivative
  作者：Mark Bahar、Ye Deng、Xiaohua Zhu、Shanshan He、Trupti Pandharkar、Mark E. Drew、Armando Navarro-Vázquez、Clemens Anklin、Roberto R. Gil、Raymond W. Doskotch、Karl A. Werbovetz、A. Douglas Kinghorn

  DOI：10.1016/j.bmcl.2011.01.101

  日期：2011.5

  Treatment of diseases such as African sleeping sickness and leishmaniasis often depends on relatively expensive or toxic drugs, and resistance to current chemotherapeutics is an issue in treating these diseases and malaria. In this study, a new semi-synthetic berberine analogue, 5,6-didehydro-8, 8-diethyl-13-oxodihydroberberine chloride (1), showed nanomolar level potency against in vitro models of leishmaniasis, malaria, and trypanosomiasis as well as activity in an in vivo visceral leishmaniasis model. Since the synthetic starting material, berberine hemisulfate, is inexpensive, 8,8-dialkyl-substituted analogues of berberine may lead to a new class of affordable antiprotozoal compounds. (C) 2011 Published by Elsevier Ltd.