prosopilosine | 1107614-74-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: prosopilosine
• 英文别名: 6,8-bis[(2R,5R,6R)-5-hydroxy-6-methylpiperidin-2-yl]decyl-[8R,8aS]-6,7-dehydroindolizidine；(2S,3R,6R)-6-[10-[(8R,8aS)-6-[10-[(2R,5R,6S)-5-hydroxy-6-methylpiperidin-2-yl]decyl]-1,2,3,5,8,8a-hexahydroindolizin-8-yl]decyl]-2-methylpiperidin-3-ol
• CAS: 1107614-74-3
• 化学式: C₄₀H₇₅N₃O₂
• 分子量: 630.054
• InChiKey: JOTBJXJGDRSICD-QVYVIMJHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  45
• 可旋转键数：
  22
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  67.8
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  prosopilosine 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以5.5 mg的产率得到prosopilosine dihydrochloride
  参考文献：
  名称：

  Indolizidine, Antiinfective and Antiparasitic Compounds from Prosopis glandulosa var. glandulosa

  摘要：

  A new potent antiinfective and antiparasitic 2,3-dihydro-1H-indolizinium chloride (1) was isolated from Prosopis glandulosa var. glandulosa. Three additional new (2-4) and one known (5) indolizidines were also isolated, and the dihydrochloride salts of 1-3 (compounds 6, 7, and 8) were prepared. Structures were determined by 1D and 2D NMR and mass spectra. Compound 1 showed potent in vitro antifungal activity against Cryptococcus neoformans and Aspergillus fumigatus (IC50 values = 0.4 and 3.0 mu g/mL, respectively) and antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare (IC50 values of 0.35 and 0.9 mu g/mL, respectively). The remarkable in vitro fungicidal activity of 1-4 against C neoformans (MFCs = 0.63-1.25 mu g/mL) and 2, 3, and 5 against A. fumigatus (MFCs = 0.63-2.5 mu g/mL) were similar to amphotericin B, but >2-4-fold more potent than 6-8. Prosopilosidine (1) showed potent in vivo activity at 0.0625 mg/kg/day/ip for 5 days in a murine model of cryptococcosis by eliminating similar to 76% of C neoformans infection from brain tissue compared to similar to 83% with amphotericin B at 1.5 mg/kg/day. Compounds 1 and 4 exhibited potent activity and high selectivity index (SI) values against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum, with IC50 values of 39 and 95 ng/mL and 42 and 120 ng/mL, respectively (chloroquine, IC50 = 17 and 140 ng/mL). Prosopilosine (1) also showed in vivo antimalarial activity, with an ED50 value of similar to 2 mg/kg/day/ip against Plasmodium berghei-infected mice after 3 days of treatment.

  DOI：

  10.1021/np800653z