6-nitro-manzamine A

• 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: 6-nitro-manzamine A
• 英文别名: 6-Nitromanzamine A；(1R,2R,4R,5Z,12R,13S,16Z)-25-(6-nitro-9H-pyrido[3,4-b]indol-1-yl)-11,22-diazapentacyclo[11.11.2.12,22.02,12.04,11]heptacosa-5,16,25-trien-13-ol
• 化学式: C₃₆H₄₃N₅O₃
• 分子量: 593.769
• InChiKey: RQLJFNBIQWTYFS-KOVQKWSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  44
• 可旋转键数：
  1
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-nitro-manzamine A 在 溶剂黄146 、 锌 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  Structure–activity relationship studies of manzamine A: Amidation of positions 6 and 8 of the β-carboline moiety

  摘要：

  Twenty manzamine amides were synthesized and evaluated for in vitro antimalarial and antimicrobial activities. The amides of manzamine A (1) showed significantly reduced cytotoxicity against Vero cells, although were less active than 1. The structure-activity analysis showed that linear, short alkyl groups adjacent to the amide carbonyl at position 8 are favored for antimalarial activity, while bulky and cyclic groups at position 6 provided the most active amides. Most of the amides showed potent activity against Mycobacterium intracellulare. The antimicrobial activity profile for position 8 series was similar to that for antimalarial activity profile, in which linear, slightly short alkyl groups adjacent to the amide carbonyl showed improved activity. Two amides 14 and 21, which showed potent antimalarial activity in vitro against Plasmodium falciparum were further evaluated in vivo in Plasmodium berghei infected mice. Oral administration of 14 and 21 at the dose of 30 mg/kg (once daily for three days) caused parasitemia suppression of 24% and 62%, respectively, with no apparent toxicity. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.09.026
• 作为产物：
  描述：

  manzamine A 在 三氟乙酸 、 sodium nitrite 作用下， 反应 1.5h， 以6 mg的产率得到6-nitro-manzamine A
  参考文献：
  名称：

  Manzamine 类似物控制神经炎症和脑感染的构效关系和作用机制研究

  摘要：

  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

  DOI：

  10.1021/jm900672t

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
• Structure–activity relationship studies of manzamine A: Amidation of positions 6 and 8 of the β-carboline moiety
  作者：Amir E. Wahba、Jiangnan Peng、Sucheta Kudrimoti、Babu L. Tekwani、Mark T. Hamann

  DOI：10.1016/j.bmc.2009.09.026

  日期：2009.11

  Twenty manzamine amides were synthesized and evaluated for in vitro antimalarial and antimicrobial activities. The amides of manzamine A (1) showed significantly reduced cytotoxicity against Vero cells, although were less active than 1. The structure-activity analysis showed that linear, short alkyl groups adjacent to the amide carbonyl at position 8 are favored for antimalarial activity, while bulky and cyclic groups at position 6 provided the most active amides. Most of the amides showed potent activity against Mycobacterium intracellulare. The antimicrobial activity profile for position 8 series was similar to that for antimalarial activity profile, in which linear, slightly short alkyl groups adjacent to the amide carbonyl showed improved activity. Two amides 14 and 21, which showed potent antimalarial activity in vitro against Plasmodium falciparum were further evaluated in vivo in Plasmodium berghei infected mice. Oral administration of 14 and 21 at the dose of 30 mg/kg (once daily for three days) caused parasitemia suppression of 24% and 62%, respectively, with no apparent toxicity. Published by Elsevier Ltd.