9-O-butyl-13-(4-isopropylbenzyl)berberine | 946576-30-3

• 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: 9-O-butyl-13-(4-isopropylbenzyl)berberine
• 英文别名: KR-72；13-(4-isopropylbenzyl)-9-O-butylberberrubine chloride；16-Butoxy-17-methoxy-21-[(4-propan-2-ylphenyl)methyl]-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-octaene;chloride
• CAS: 946576-30-3
• 化学式: C₃₃H₃₆NO₄*Cl
• 分子量: 546.106
• InChiKey: YDEQGPBVDZZGMV-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  40.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  盐酸小檗碱 在 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 26.0h， 生成 9-O-butyl-13-(4-isopropylbenzyl)berberine
  参考文献：
  名称：

  9-O-butyl-13-(4-isopropylbenzyl)berberine, KR-72, Is a Potent Antifungal Agent That Inhibits the Growth of Cryptococcus neoformans by Regulating Gene Expression

  摘要：

  在这项研究中，我们探索了 KR-72 的作用模式，KR-72 是一种 9-O-丁基-13-（4-异丙基苄基）小檗碱衍生物，以前曾被证明对多种人类真菌病原体具有很强的抗真菌活性。DNA 微阵列数据显示，KR-72 的处理显著改变了 C. neoformans 的转录谱，影响了 2000 多个基因的表达。参与翻译和转录的基因大多上调，而参与细胞骨架、细胞内运输和脂质代谢的基因则下调。KR-72 还与抗真菌剂 FK506 具有很强的协同作用。KR-72 处理调节了几个重要基因的表达，包括 ECM16、NOP14、HSP10 和 MGE1，这些基因是 C. neoformans 生长所必需的。KR-72 介导的 MGE1 诱导还可能通过损害细胞周期或 DNA 修复系统来降低 C. neoformans 的活力。总之，KR-72 通过调节不同的生物过程显示出抗真菌活性，其作用模式与临床上可用的抗真菌药物（如多烯类和唑类药物）不同。

  DOI：

  10.1371/journal.pone.0109863

文献信息

• Berberrubine Derivatives Having Antifungal Activities
  申请人：Kim Sung Uk

  公开号：US20100292476A1

  公开（公告）日：2010-11-18

  The present invention relates to a berberrubine derivative having superior antifungal activity, more particularly to a berberrubine derivative having inhibitory activity against chitin synthase, which participates in the synthesis of chitin and is essential in the growth of fungi, and having a potent antifungal activity against human pathogenic fungi.

  本发明涉及一种具有优越抗真菌活性的小檗碱衍生物，更具体地说，涉及一种对壳聚糖合酶具有抑制活性的小檗碱衍生物，该酶参与壳聚糖的合成，在真菌生长中是必不可少的，并且对人类致病真菌具有强大的抗真菌活性。
• Synthesis and antifungal activity of a novel series of 13-(4-isopropylbenzyl)berberine derivatives
  作者：Ki Duk Park、Sung Jin Cho、Jae Sun Moon、Sung Uk Kim

  DOI：10.1016/j.bmcl.2010.09.045

  日期：2010.11

  By replacing the methyl group of 13-(4-isopropylbenzyl)berberine 2 with various acyl, alkyl, and benzyl groups via the demethylated intermediate, 13-(4-isopropylbenzyl) berberrubine 4, a novel series of 9-O-alkyl-13-(4-isopropylbenzyl)berberine derivatives was synthesized and examined for antifungal activities against various human pathogenic fungi. The introduction of various alkyl groups led to enhanced antifungal activity but that of acyl groups resulted in decrease of the activity. Among them, 9-O-butyl-13-(4-isopropylbenzyl)berberine 6d exhibited the most potent antifungal activities against Cryptococcus neoformans, Candida species (MIC = 0.25-1 mu g/ml), and Aspergillus species (MIC = 2-4 mu g/ml). The compound was found to be relatively safe up to 900 mg/kg in oral administration to mice. (C) 2010 Elsevier Ltd. All rights reserved.
• 9-O-butyl-13-(4-isopropylbenzyl)berberine, KR-72, Is a Potent Antifungal Agent That Inhibits the Growth of Cryptococcus neoformans by Regulating Gene Expression
  作者：Soohyun Bang、Hyojeong Kwon、Hyun Sook Hwang、Ki Duk Park、Sung Uk Kim、Yong-Sun Bahn

  DOI：10.1371/journal.pone.0109863

  日期：——

  In this study we explored the mode of action of KR-72, a 9-O-butyl-13-(4-isopropylbenzyl)berberine derivative previously shown to exhibit potent antifungal activity against a variety of human fungal pathogens. The DNA microarray data revealed that KR-72 treatment significantly changed the transcription profiles of C. neoformans, affecting the expression of more than 2,000 genes. Genes involved in translation and transcription were mostly upregulated, whereas those involved in the cytoskeleton, intracellular trafficking, and lipid metabolism were downregulated. KR-72 also exhibited a strong synergistic effect with the antifungal agent FK506. KR-72 treatment regulated the expression of several essential genes, including ECM16, NOP14, HSP10 and MGE1, which are required for C. neoformans growth. The KR-72-mediated induction of MGE1 also likely reduced the viability of C. neoformans by impairing cell cycle or the DNA repair system. In conclusion, KR-72 showed antifungal activity by modulating diverse biological processes through a mode of action distinct from those of clinically available antifungal drugs such as polyene and azole drugs.

  在这项研究中，我们探索了 KR-72 的作用模式，KR-72 是一种 9-O-丁基-13-（4-异丙基苄基）小檗碱衍生物，以前曾被证明对多种人类真菌病原体具有很强的抗真菌活性。DNA 微阵列数据显示，KR-72 的处理显著改变了 C. neoformans 的转录谱，影响了 2000 多个基因的表达。参与翻译和转录的基因大多上调，而参与细胞骨架、细胞内运输和脂质代谢的基因则下调。KR-72 还与抗真菌剂 FK506 具有很强的协同作用。KR-72 处理调节了几个重要基因的表达，包括 ECM16、NOP14、HSP10 和 MGE1，这些基因是 C. neoformans 生长所必需的。KR-72 介导的 MGE1 诱导还可能通过损害细胞周期或 DNA 修复系统来降低 C. neoformans 的活力。总之，KR-72 通过调节不同的生物过程显示出抗真菌活性，其作用模式与临床上可用的抗真菌药物（如多烯类和唑类药物）不同。