5-[[2-(Diethylamino)ethyl]amino]-8-methoxyimidazo[4,5,1-de] acridin-6-one Dihydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-[[2-(Diethylamino)ethyl]amino]-8-methoxyimidazo[4,5,1-de] acridin-6-one Dihydrochloride
• 英文别名: 10-[2-(diethylamino)ethylamino]-5-methoxy-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2(7),3,5,9,11,13(16),14-heptaen-8-one;hydrochloride
• 化学式: C₂₁H₂₄N₄O₂*2ClH
• 分子量: 437.369
• InChiKey: OCSLOHWPQDAQEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.62
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  59.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-<<2-(diethylamino)ethyl>amino>-8-methoxy-6H-imidazo<4,5,1-de>acridin-6-one 在 盐酸 作用下， 以 甲醇 、 乙醚 、 氯仿 为溶剂， 生成 5-[[2-(Diethylamino)ethyl]amino]-8-methoxyimidazo[4,5,1-de] acridin-6-one Dihydrochloride
  参考文献：
  名称：

  Photodynamic Inactivation of Candida albicans with Imidazoacridinones: Influence of Irradiance, Photosensitizer Uptake and Reactive Oxygen Species Generation

  摘要：

  抗真菌治疗的适用性不断增加、可用药物类别的范围有限以及念珠菌属中耐药性的出现。表明需要新的治疗方案。为了探索白色念珠菌光灭活的适用性，我们研究了九种结构不同的咪唑吖啶酮衍生物作为光敏剂。最有效的衍生物显示活细胞数量减少了 104 倍以上。比较了三种最活性化合物在不同辐射功率（3.5至63 mW/cm2）下的杀菌作用，分析表明7 mW/cm2是最有效的。这些化合物在真菌细胞中的细胞内积累与所有 9 种衍生物的杀菌活性相关。维拉帕米（一种针对念珠菌 ABC 外排泵的抑制剂）缺乏作用，表明这些咪唑吖啶酮不是 ABC 转运蛋白的底物。因此，与唑类（用于对抗念珠菌的主要抗真菌药物）不同，ABC 转运蛋白介导的耐药性不太可能。电子顺磁共振（EPR）-自旋捕获数据表明，这些衍生物的光诱导杀菌作用可能取决于超氧阴离子的产生。观察到超氧阴离子的最高生成速率为 1330H、1610H 和 1611。在用紫外激光照射咪唑吖啶酮衍生物时也检测到单线态氧的产生，根据化合物的类型，单线态氧的产率从低到中等。因此，本研究中检测的咪唑吖啶酮衍生物可能通过混合I型/II型光动力机制起作用。所提供的数据表明所研究的咪唑吖啶酮的结构、细胞杀伤能力和ROS产生之间缺乏直接相关性。然而，我们首次表明，咪唑吖啶酮不仅在细胞内积累是白色念珠菌致命光敏化的必要先决条件，而且还定位在特定的细胞结构内。我们的研究结果表明 IA 衍生物作为有效的抗真菌光敏剂，有可能用于念珠菌感染的局部治疗。

  DOI：

  10.1371/journal.pone.0129301

文献信息

• Imidazoacridinone derivative compounds and methods for their use
  申请人：Assaraf Yehuda G.

  公开号：US20100137351A1

  公开（公告）日：2010-06-03

  The present invention provides IA derivative compounds of the formula: where the variables are described herein.

  本发明提供了公式为的IA衍生物化合物：其中变量如本文所述。
• Chromophore-modified antineoplastic imidazoacridinones. Synthesis and activity against murine leukemias
  作者：Wieslaw M. Cholody、Sante Martelli、Jerzy Konopa

  DOI：10.1021/jm00080a026

  日期：1992.1

  The synthesis of 8-hydroxy and 8-methoxy analogues of some substituted 5-aminoimidazoacridinones (4) is described. The synthesis was carried out by a three-step sequence from the corresponding 1-chloro-4-nitro-9(10H)-acridinone precursors (1). The annulation of the imidazolo ring onto the aminoacridinone chromophore was accomplished by heating the required aminoacridinone (3) with formic acid or, in the case of 1-methyl derivatives, with N,N-dimethylacetamide. Potent cytotoxic activity against L1210 leukemia, as well as antitumor activity against P388 leukemia in mice, was demonstrated for the 8-hydroxy analogues. The corresponding 8-methoxy derivatives were not cytotoxic. However, in some cases, they showed significant in vivo antileukemic activity.
• Photodynamic Inactivation of Candida albicans with Imidazoacridinones: Influence of Irradiance, Photosensitizer Uptake and Reactive Oxygen Species Generation
  作者：Aleksandra Taraszkiewicz、Grzegorz Szewczyk、Tadeusz Sarna、Krzysztof P. Bielawski、Joanna Nakonieczna

  DOI：10.1371/journal.pone.0129301

  日期：——

  The increasing applicability of antifungal treatments, the limited range of available drug classes and the emergence of drug resistance in Candida spp. suggest the need for new treatment options. To explore the applicability of C. albicans photoinactivation, we examined nine structurally different imidazoacridinone derivatives as photosensitizing agents. The most effective derivatives showed a >104-fold reduction of viable cell numbers. The fungicidal action of the three most active compounds was compared at different radiant powers(3.5 to 63 mW/cm2), and this analysis indicated that 7 mW/cm2 was the most efficient. The intracellular accumulation of these compounds in fungal cells correlated with the fungicidal activity of all 9 derivatives. The lack of effect of verapamil, an inhibitor targeting Candida ABC efflux pumps, suggests that these imidazoacridinones are not substrates for ABC transporters. Thus, unlike azoles, a major class of antifungals used against Candida, ABC transporter-mediated resistance is unlikely. Electron paramagnetic resonance (EPR)-spin trapping data suggested that the fungicidal light-induced action of these derivatives might depend on the production of superoxide anion. The highest generation rate of superoxide anion was observed for 1330H, 1610H, and 1611. Singlet oxygen production was also detected upon the irradiation of imidazoacridinone derivatives with UV laser light, with a low to moderate yield, depending on the type of compound. Thus, imidazoacridinone derivatives examined in the present study might act via mixed type I/type II photodynamic mechanism. The presented data indicate lack of direct correlation between the structures of studied imidazoacridinones, cell killing ability, and ROS production. However, we showed for the first time that for imidazoacridinones not only intracellular accumulation is necessary prerequisite of lethal photosensitization of C. albicans, but also localization within particular cellular structures. Our findings present IA derivatives as efficient antifungal photosensitizers with a potential to be used in local treatment of Candida infection.

  抗真菌治疗的适用性不断增加、可用药物类别的范围有限以及念珠菌属中耐药性的出现。表明需要新的治疗方案。为了探索白色念珠菌光灭活的适用性，我们研究了九种结构不同的咪唑吖啶酮衍生物作为光敏剂。最有效的衍生物显示活细胞数量减少了 104 倍以上。比较了三种最活性化合物在不同辐射功率（3.5至63 mW/cm2）下的杀菌作用，分析表明7 mW/cm2是最有效的。这些化合物在真菌细胞中的细胞内积累与所有 9 种衍生物的杀菌活性相关。维拉帕米（一种针对念珠菌 ABC 外排泵的抑制剂）缺乏作用，表明这些咪唑吖啶酮不是 ABC 转运蛋白的底物。因此，与唑类（用于对抗念珠菌的主要抗真菌药物）不同，ABC 转运蛋白介导的耐药性不太可能。电子顺磁共振（EPR）-自旋捕获数据表明，这些衍生物的光诱导杀菌作用可能取决于超氧阴离子的产生。观察到超氧阴离子的最高生成速率为 1330H、1610H 和 1611。在用紫外激光照射咪唑吖啶酮衍生物时也检测到单线态氧的产生，根据化合物的类型，单线态氧的产率从低到中等。因此，本研究中检测的咪唑吖啶酮衍生物可能通过混合I型/II型光动力机制起作用。所提供的数据表明所研究的咪唑吖啶酮的结构、细胞杀伤能力和ROS产生之间缺乏直接相关性。然而，我们首次表明，咪唑吖啶酮不仅在细胞内积累是白色念珠菌致命光敏化的必要先决条件，而且还定位在特定的细胞结构内。我们的研究结果表明 IA 衍生物作为有效的抗真菌光敏剂，有可能用于念珠菌感染的局部治疗。