(2E,2'E)-3,3'-(6,6'-bis(allyloxy)-5,5'-dimethoxy-[1,1'-biphenyl]-3,3'-diyl)bis(1-(4-chlorophenyl)prop-2-en-1-one)

• 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: (2E,2'E)-3,3'-(6,6'-bis(allyloxy)-5,5'-dimethoxy-[1,1'-biphenyl]-3,3'-diyl)bis(1-(4-chlorophenyl)prop-2-en-1-one)
• 英文别名: (E)-1-(4-chlorophenyl)-3-[3-[5-[(E)-3-(4-chlorophenyl)-3-oxoprop-1-enyl]-3-methoxy-2-prop-2-enoxyphenyl]-5-methoxy-4-prop-2-enoxyphenyl]prop-2-en-1-one
• 化学式: C₃₈H₃₂Cl₂O₆
• 分子量: 655.574
• InChiKey: FMKVGNPYKMIATM-ZEELXFFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6,6-二羟基-5,5-二甲氧基-(1,1-联苯-基)-3,3-二甲醛 在 potassium carbonate 、 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 生成 (2E,2'E)-3,3'-(6,6'-bis(allyloxy)-5,5'-dimethoxy-[1,1'-biphenyl]-3,3'-diyl)bis(1-(4-chlorophenyl)prop-2-en-1-one)
  参考文献：
  名称：

  Facile synthesis of vanillin-based novel bischalcones identifies one that induces apoptosis and displays synergy with Artemisinin in killing chloroquine resistant Plasmodium falciparum

  摘要：

  The inherent affinity of natural compounds for biological receptors has been comprehensively exploited with great success for the development of many drugs, including antimalarials. Here the natural flavoring compound vanillin has been used as an economical precursor for the synthesis of a series of novel bischalcones whose in vitro antiplasmodial activities have been evaluated against erythrocytic stages of Plasmodium falciparum. Bischalcones 9, 11 and 13 showed promising antiplasmodial activity (Chloroquine (CQ) sensitive Pf3D7 IC50 (mu M): 2.0, 1.5 and 2.5 respectively)but only 13 displayed potent activities also against CQ resistant PfDd2 and PfIndo strains exhibiting resistance indices of 1.4 and 1.5 respectively. IC90 (8 mu M) of 13 showed killing activity against ring, trophozoite and schizont stages. Further, 13 initiated the cascade of reactions that culminates in programmed cell death of parasites including trans location of phosphatidylserine from inner to outer membrane leaflet, loss of mitochondrial membrane potential, activation of caspase like enzyme, DNA fragmentation and chromatin condensation. The combinations of 13 + Artemisinin (ART) exhibited strong synergy (Sigma FIC50:0.46 to 0.58) while 13 + CQ exhibited mild synergy (Sigma FIC50,: 0.7 to 0.98) to mild antagonism (Sigma FIC50: 1.08 to 1.23) against PfIndo. In contrast, both combinations showed marked antagonism against Pf3D7(Sigma FIC50: 133 to 3.34). These features of apoptosis and strong synergy with Artemisinin suggest that bischalcones possess promising antimalarial drug-like properties and may also act as a good partner drugs for artemisinin based combination therapies (ACTs) against Chloroquine resistant P. falciparum. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.06.025

文献信息

• Facile synthesis of vanillin-based novel bischalcones identifies one that induces apoptosis and displays synergy with Artemisinin in killing chloroquine resistant Plasmodium falciparum
  作者：Upendra K. Sharma、Dinesh Mohanakrishnan、Nandini Sharma、Danish Equbal、Dinkar Sahal、Arun K. Sinha

  DOI：10.1016/j.ejmech.2018.06.025

  日期：2018.7

  The inherent affinity of natural compounds for biological receptors has been comprehensively exploited with great success for the development of many drugs, including antimalarials. Here the natural flavoring compound vanillin has been used as an economical precursor for the synthesis of a series of novel bischalcones whose in vitro antiplasmodial activities have been evaluated against erythrocytic stages of Plasmodium falciparum. Bischalcones 9, 11 and 13 showed promising antiplasmodial activity (Chloroquine (CQ) sensitive Pf3D7 IC50 (mu M): 2.0, 1.5 and 2.5 respectively)but only 13 displayed potent activities also against CQ resistant PfDd2 and PfIndo strains exhibiting resistance indices of 1.4 and 1.5 respectively. IC90 (8 mu M) of 13 showed killing activity against ring, trophozoite and schizont stages. Further, 13 initiated the cascade of reactions that culminates in programmed cell death of parasites including trans location of phosphatidylserine from inner to outer membrane leaflet, loss of mitochondrial membrane potential, activation of caspase like enzyme, DNA fragmentation and chromatin condensation. The combinations of 13 + Artemisinin (ART) exhibited strong synergy (Sigma FIC50:0.46 to 0.58) while 13 + CQ exhibited mild synergy (Sigma FIC50,: 0.7 to 0.98) to mild antagonism (Sigma FIC50: 1.08 to 1.23) against PfIndo. In contrast, both combinations showed marked antagonism against Pf3D7(Sigma FIC50: 133 to 3.34). These features of apoptosis and strong synergy with Artemisinin suggest that bischalcones possess promising antimalarial drug-like properties and may also act as a good partner drugs for artemisinin based combination therapies (ACTs) against Chloroquine resistant P. falciparum. (C) 2018 Elsevier Masson SAS. All rights reserved.