N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-acetylbetulinamide | 1422437-56-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-acetylbetulinamide
• 英文别名: [(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-[3-[4-(3-aminopropyl)piperazin-1-yl]propylcarbamoyl]-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl] acetate
• CAS: 1422437-56-6
• 化学式: C₄₂H₇₂N₄O₃
• 分子量: 681.059
• InChiKey: VBZKHGGXJRWMHP-YVXNQENWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  49
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  87.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  白桦脂酸 在 吡啶 、 草酰氯 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 57.0h， 生成 N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-acetylbetulinamide
  参考文献：
  名称：

  Synthesis and Antiplasmodial Activity of Betulinic Acid and Ursolic Acid Analogues

  摘要：

  全球超过40%的人口面临疟疾感染的风险，该病主要影响热带和亚热带地区的贫困人口。疟疾治疗广泛使用从植物中提取的产品，如奎宁和青蒿素及其衍生物。然而，全球使用这些抗疟药物导致抗药性寄生虫的传播，增加了疟疾的发病率和死亡率。鉴于文献显示三萜类化合物，特别是白桦脂酸（1）和熊果酸（2）的抗疟潜力，本研究探讨了一些新的1和2衍生物，在C-3和C-28位置进行修饰后，对氯喹敏感的恶性疟原虫3D7株的抗疟活性。抗疟研究采用了流式细胞术和荧光光谱分析，使用YOYO-1、二氢乙锭和Fluo4/AM进行染色。在获得的六个类似物中，化合物1c和2c显示出优异的活性（IC50分别为220和175 nM），而1a和1b显示出良好的活性（IC50分别为4和5 μM）。在评估对HEK293T细胞的细胞毒性后，1a无毒性，而1c和2c的IC50为4 μM，选择性指数（SI）值分别为18和23。此外，抗疟活性最佳的化合物2c涉及钙调节途径。

  DOI：

  10.3390/molecules171012003

文献信息

• Synthesis of Isosteric Triterpenoid Derivatives and Antifungal Activity
  作者：Adrine Innocente、Bruna B. Casanova、Fernanda Klein、Aline D. Lana、Dariane Pereira、Mauro N. Muniz、Pascal Sonnet、Grace Gosmann、Alexandre M. Fuentefria、Simone C. B. Gnoatto

  DOI：10.1111/cbdd.12251

  日期：2014.3

  Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. There is an urgent need to develop efficient and non‐toxic antimycotic agents with a specific spectrum of activity. Triterpenes have been demonstrated to exhibit a wide range of biological activities, including antifungal activities. In this study, through hemisynthesis, we aimed to obtain triterpene‐isosteric molecules from betulinic and ursolic acids to improve the antifungal activity and spectrum of action of these compounds. Six compounds were resynthesized and tested against eleven mucocutaneous and cutaneous mycotic agents. The results of the susceptibility assays were expressed as the minimal inhibitory concentration (MIC). The MIC values of the piperazinyl derivatives of ursolic and betulinic acids that were active against pathogenic yeasts were in the range of 16–32 μg/mL and 4–16 μg/mL, respectively, whereas fungicidal effects were observed at concentrations ranging from 16 to 128 μg/mL and 8 to 128 μg/mL, respectively. The piperazinyl derivative of betulinic acid exhibited an antifungal profile similar to that of terbinafine and was the most effective derivative against dermatophytes. This strategy led to a promising candidate for the development of a new antifungal agent.