Manzamine F | 107900-75-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: Manzamine F
• 英文别名: (1R,2R,4S,12R,13S,16Z)-13-hydroxy-25-(8-hydroxy-9H-pyrido[3,4-b]indol-1-yl)-11,22-diazapentacyclo[11.11.2.12,22.02,12.04,11]heptacosa-16,25-dien-7-one
• CAS: 107900-75-4
• 化学式: C₃₆H₄₄N₄O₃
• 分子量: 580.77
• InChiKey: KYLZDBBEWRTKTG-PYBBOEBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  43
• 可旋转键数：
  1
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  92.7
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Manzamine F 在 溶剂黄146 、 三氟乙酸 、 锌 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.67h， 生成 7-ethylaminomanzamine F
  参考文献：
  名称：

  Reductive N-Alkylation of Nitroarenes: A Green Approach for the N-Alkylation of Natural Products

  摘要：

  A simple, mild, cost-effective, and green approach for the reductive mono-N-alkylation of nitroarenes has been developed. HOAc/Zn are utilized as the reducing system together with a carbonyl compound as an alkyl source in methanol. Excellent yields were obtained with stoichiometric control of mono- over dialkylated products. Application to five complex natural products demonstrated the practical utility of the method.

  DOI：

  10.1021/jo300303d

文献信息

• Structure−Activity Relationship and Mechanism of Action Studies of Manzamine Analogues for the Control of Neuroinflammation and Cerebral Infections
  作者：Jiangnan Peng、Sucheta Kudrimoti、Sivaprakasam Prasanna、Srinivas Odde、Robert J. Doerksen、Hari K Pennaka、Yeun-Mun Choo、Karumanchi V. Rao、Babu L. Tekwani、Vamsi Madgula、Shabana I. Khan、Bin Wang、Alejandro M. S. Mayer、Melissa R. Jacob、Lan Chun Tu、Jürg Gertsch、Mark T. Hamann

  DOI：10.1021/jm900672t

  日期：2010.1.14

  Structure−activity relationship studies were carried out by chemical modification of manzamine A (1), 8-hydroxymanzamine A (2), manzamine F (14), and ircinal isolated from the sponge Acanthostrongylophora. The derived analogues were evaluated for antimalarial, antimicrobial, and antineuroinflammatory activities. Several modified products exhibited potent and improved in vitro antineuroinflammatory, antimicrobial

  构效关系研究是通过对曼扎明 A ( 1 )、8-羟基曼扎明A ( 2 )、曼扎明 F ( 14 ) 和从海绵棘圆线虫中分离的 ircinal 进行化学修饰来进行的。对衍生类似物的抗疟、抗微生物和抗神经炎症活性进行了评估。几种改良产品在体外表现出有效和改进的抗神经炎症、抗菌和抗疟活性。在多剂量和单剂量体内实验中，与氯喹相比，图1对疟疾的活性有所提高。小鼠疟疾的 100% 治愈率揭示了显着的抗疟潜力，一次给药 100 mg/kg 的1. Manzamines 的强效抗神经炎症活性将为预防和治疗脑部感染（例如，隐球菌和疟原虫）提供巨大的益处。此外，在使用 MDR-MDCK 单层的体外模型中，1显示可渗透穿过血脑屏障 (BBB)。对接研究支持2与糖原合成激酶-3β (GSK-3β) 的 ATP 非竞争性口袋结合，这是 manzamines 的推定目标。基于此处介绍的结果，将有可能围绕这种天然产物支
• Glycogen Synthase Kinase-3 (GSK-3) Inhibitory Activity and Structure–Activity Relationship (SAR) Studies of the Manzamine Alkaloids. Potential for Alzheimer’s Disease
  作者：Mark Hamann、Diana Alonso、Ester Martín-Aparicio、Ana Fuertes、M. José Pérez-Puerto、Ana Castro、Susana Morales、María Luisa Navarro、María del Monte-Millán、Miguel Medina、Hari Pennaka、Akula Balaiah、Jiangnan Peng、Jennifer Cook、Subagus Wahyuono、Ana Martínez

  DOI：10.1021/np060092r

  日期：2007.9.1

  Manzamine A and related derivatives isolated from a common Indonesian sponge, Acanthostrongylophora, have been identified as a new class of GSK-3 beta inhibitors. The semisynthesis of new analogues and the first structure-activity relationship studies with GSK-3 beta are also reported. Moreover, manzamine A proved to be effective in decreasing tau hyperphosphorylation in human neuroblastoma cell lines, a demonstration of its ability to enter cells and interfere with tau pathology. Inhibition studies of manzamine A against a selected panel of five different kinases related to GSK-3 beta, specifically CDK-1, PKA, CDK-5, MAPK, and GSK-3 alpha, show the specific inhibition of manzamine A on GSK-3 beta and CDK-5, the two kinases involved in tau pathological hyperphosphorylation. These results suggest that manzamine A constitutes a promising scaffold from which more potent and selective GSK-3 inhibitors could be designed as potential therapeutic agents for Alzheimer's disease.