(E)-3-(3-(2,5-dimethoxyphenyl)acryloyl)-2H-chromen-2-one | 1242240-53-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3-(2,5-dimethoxyphenyl)acryloyl)-2H-chromen-2-one
• 英文别名: 3-[(E)-3-(2,5-dimethoxyphenyl)prop-2-enoyl]chromen-2-one
• CAS: 1242240-53-4
• 化学式: C₂₀H₁₆O₅
• 分子量: 336.344
• InChiKey: DNDNIKUCJZVDTP-VQHVLOKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-乙酰基香豆素 、 2,5-二甲氧基苯甲醛 在 silica sulfuric acid 作用下， 以72%的产率得到(E)-3-(3-(2,5-dimethoxyphenyl)acryloyl)-2H-chromen-2-one
  参考文献：
  名称：

  Synthesis of novel α-pyranochalcones and pyrazoline derivatives as Plasmodium falciparum growth inhibitors

  摘要：

  Both the lack of a credible malaria vaccine and the emergence and spread of parasites resistant to most of the clinically used antimalarial drugs and drug combination have aroused an imperative need to develop new drugs against malaria. In present work, alpha-pyranochalcones and pyrazoline analogs were synthesized to discover chemically diverse antimalarial leads. Compounds were tested for antimalarial activity by evaluation of the growth of malaria parasite in culture using the microtiter plate based SYBR-Green-I assay. The (E)-3-(3-(2,3,4-trimethoxyphenyl)-acryloyl)-2H-chromen-2-one (Ga6) turned out to be the most potent analog of the series, showing IC(50) of 3.1 mu g/ml against chloroquine-sensitive (3D7) strain and IC(50) of 1.1 mu g/ml against chloroquine-resistant field isolate (RKL9) of Plasmodium falciparum. Cytotoxicity study of the most potent compounds was also performed against HeLa cell line using the MTT assay. All the tested compounds showed high therapeutic indices suggesting that they were selective in their action against the malaria parasite. Furthermore, docking of Ga6 into active site of falcipain enzyme revealed its predicted interactions with active site residues. This is the first instance wherein chromeno-pyrazolines have been found to be active antimalarial agents. Further exploration and optimization of this new lead could provide novel, antimalarial molecules which can ward off issues of cross-resistance to drugs like chloroquine. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.05.069

文献信息

• Synthesis of novel α-pyranochalcones and pyrazoline derivatives as Plasmodium falciparum growth inhibitors
  作者：Gajanan Wanare、Rahul Aher、Neha Kawathekar、Ravi Ranjan、Naveen Kumar Kaushik、Dinkar Sahal

  DOI：10.1016/j.bmcl.2010.05.069

  日期：2010.8

  Both the lack of a credible malaria vaccine and the emergence and spread of parasites resistant to most of the clinically used antimalarial drugs and drug combination have aroused an imperative need to develop new drugs against malaria. In present work, alpha-pyranochalcones and pyrazoline analogs were synthesized to discover chemically diverse antimalarial leads. Compounds were tested for antimalarial activity by evaluation of the growth of malaria parasite in culture using the microtiter plate based SYBR-Green-I assay. The (E)-3-(3-(2,3,4-trimethoxyphenyl)-acryloyl)-2H-chromen-2-one (Ga6) turned out to be the most potent analog of the series, showing IC(50) of 3.1 mu g/ml against chloroquine-sensitive (3D7) strain and IC(50) of 1.1 mu g/ml against chloroquine-resistant field isolate (RKL9) of Plasmodium falciparum. Cytotoxicity study of the most potent compounds was also performed against HeLa cell line using the MTT assay. All the tested compounds showed high therapeutic indices suggesting that they were selective in their action against the malaria parasite. Furthermore, docking of Ga6 into active site of falcipain enzyme revealed its predicted interactions with active site residues. This is the first instance wherein chromeno-pyrazolines have been found to be active antimalarial agents. Further exploration and optimization of this new lead could provide novel, antimalarial molecules which can ward off issues of cross-resistance to drugs like chloroquine. (C) 2010 Elsevier Ltd. All rights reserved.