10-dihydroartemisinyl-4-[(1E)-3-oxo-3-(2,3,4-trichlorophenyl)prop-1-en-1-yl]benzoate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 10-dihydroartemisinyl-4-[(1E)-3-oxo-3-(2,3,4-trichlorophenyl)prop-1-en-1-yl]benzoate
• 英文别名: [(1S,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl] 4-[(E)-3-oxo-3-(2,3,4-trichlorophenyl)prop-1-enyl]benzoate
• 化学式: C₃₁H₃₁Cl₃O₇
• 分子量: 621.942
• InChiKey: RNGJCYWLZLBIIF-AWKMOREJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2',3',4'-三氯苯乙酮 在 草酰氯 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 17.25h， 生成 10-dihydroartemisinyl-4-[(1E)-3-oxo-3-(2,3,4-trichlorophenyl)prop-1-en-1-yl]benzoate
  参考文献：
  名称：

  Synthesis and in vitro biological evaluation of dihydroartemisinyl-chalcone esters

  摘要：

  A series of dihydroartemisinyl-chalcone esters were synthesized through esterification of chalcones with dihydroartemisinin (DHA). The hybrids were screened against chloroquine (CQ) sensitive (3D7) and CQ resistant (W2) strains of intraerythrocytic Plasmodium falciparum parasites, and were all found to be active, with IC50 values ranging between 1.5 and 11 nM against both strains, with SI values over 5800. The esters featuring oxygenated aryl rings (7,10 and 11), were found to be equipotent to DHA, but were 2-3 times more active than artesunate against the 3D7 and W2 strains of the malaria parasites. They were also screened in vitro against a panel of three cancer cell lines consisting of TK-10, UACC-62 and MCF-7. Compound 7, bearing a furan ring, displayed the most potent overall antitumor activity against all three cancer cell lines. TGA revealed that the targeted hybrids were all thermally more stable than DHA, which may be beneficial to the high temperature storage conditions that prevail in malaria endemic countries. During this study, ester 7 was identified as the best candidate for further investigation as a potential drug in search for new, safe and effective antimalarial drugs. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.016

文献信息

• Synthesis and in vitro biological evaluation of dihydroartemisinyl-chalcone esters
  作者：Frans J. Smit、Riëtte A. van Biljon、Lyn-Marie Birkholtz、David D. N'Da

  DOI：10.1016/j.ejmech.2014.11.016

  日期：2015.1

  A series of dihydroartemisinyl-chalcone esters were synthesized through esterification of chalcones with dihydroartemisinin (DHA). The hybrids were screened against chloroquine (CQ) sensitive (3D7) and CQ resistant (W2) strains of intraerythrocytic Plasmodium falciparum parasites, and were all found to be active, with IC50 values ranging between 1.5 and 11 nM against both strains, with SI values over 5800. The esters featuring oxygenated aryl rings (7,10 and 11), were found to be equipotent to DHA, but were 2-3 times more active than artesunate against the 3D7 and W2 strains of the malaria parasites. They were also screened in vitro against a panel of three cancer cell lines consisting of TK-10, UACC-62 and MCF-7. Compound 7, bearing a furan ring, displayed the most potent overall antitumor activity against all three cancer cell lines. TGA revealed that the targeted hybrids were all thermally more stable than DHA, which may be beneficial to the high temperature storage conditions that prevail in malaria endemic countries. During this study, ester 7 was identified as the best candidate for further investigation as a potential drug in search for new, safe and effective antimalarial drugs. (C) 2014 Elsevier Masson SAS. All rights reserved.