(5Z)-5-[[3-bromo-4-[(4-methylphenyl)methoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (5Z)-5-[[3-bromo-4-[(4-methylphenyl)methoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one
• 化学式: C₁₈H₁₄BrNO₂S₂
• 分子量: 420.351
• InChiKey: VUGOPEQLAGAKLC-SXGWCWSVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  95.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-溴-4-羟基苯甲醛 、 4-甲基氯苄 在 potassium carbonate 、 溶剂黄146 、 potassium iodide 、 β-丙氨酸 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 (5Z)-5-[[3-bromo-4-[(4-methylphenyl)methoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one
  参考文献：
  名称：

  Design and synthesis of new drugs inhibitors of Candida albicans hyphae and biofilm formation by upregulating the expression of TUP1 transcription repressor gene

  摘要：

  Candida albicans is a common human fungal pathogen that causes disease ranging from superficial to lethal infections. C. albicans grows as budding yeast which can transform into hyphae in response to various environmental or biological stimuli. Although both forms have been associated with virulence, the hyphae form is responsible for the formation of multi-drug resistance biofilm. Here, new compounds were designed to selectively inhibit C. albicans hyphae formation without affecting human cells to afford sufficient safety. The newly designed 5-[3-substitued-4-(4-substituedbenzyloxy)-benzylidene]-2-thioxo-thiazolidin-4-one derivatives, named SR, showed very specific and effective inhibition activity against C. albicans hyphae formation. SR compounds caused hyphae inhibition activity at concentrations 10-40 fold lower than the concentration required to inhibit Candida yeast and bacterial growths. The anti-hyphae inhibition activities of SR compounds were via activation of the hyphae transcription repressor gene, TUP1. Correlation studies between the expression of TUP1 gene and the activity of SR compounds confirmed that the anti-C. albicans activities of SR compounds were via inhibition of hyphae formation. The newly designed SR compounds showed 10-40% haemolytic activity on human erythrocytes when compared to 100% haemolysis by 0.1% triton employed as positive control. Furthermore, theoretical prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of SR compounds confirmed their safety, efficient metabolism and possible oral bioavailability. With the minimal toxicity and significant activity of the newly-designed SR compounds, a future optimization of pharmaceutical formulation may develop a promising inhibitor of hyphal formation not only for C. albicans but also for other TUP1- dependent dimorphic fungal infections.

  DOI：

  10.1016/j.ejps.2020.105327

文献信息

• Small Molecule Inhibitors of Fungal Hyphae and Biofilm Formation
  申请人：University of Sharjah

  公开号：US20210179571A1

  公开（公告）日：2021-06-17

  Novel compounds having inhibitory activity on the formation of fungal hyphae and biofilms, and therapeutic formulations and methods based on the novel inhibitors.
• [EN] SMALL MOLECULE INHIBITORS OF FUNGAL HYPHAE AND BIOFILM FORMATION<br/>[FR] INHIBITEURS À PETITES MOLÉCULES DE LA FORMATION D'HYPHES FONGIQUES ET DE BIOFILMS
  申请人：UNIV OF SHARJAH

  公开号：WO2021117014A2

  公开（公告）日：2021-06-17

  Novel compounds having inhibitory activity on the formation of fungal hyphae and biofilms, and therapeutic formulations and methods based on the novel inhibitors.
• Design and synthesis of new drugs inhibitors of Candida albicans hyphae and biofilm formation by upregulating the expression of TUP1 transcription repressor gene
  作者：Rania Hamdy、Sameh S.M. Soliman、Abrar I. Alsaadi、Bahgat Fayed、Alshaimaa M. Hamoda、Samia A. Elseginy、Mohamed I. Husseiny、Ashraf S. Ibrahim

  DOI：10.1016/j.ejps.2020.105327

  日期：2020.5

  Candida albicans is a common human fungal pathogen that causes disease ranging from superficial to lethal infections. C. albicans grows as budding yeast which can transform into hyphae in response to various environmental or biological stimuli. Although both forms have been associated with virulence, the hyphae form is responsible for the formation of multi-drug resistance biofilm. Here, new compounds were designed to selectively inhibit C. albicans hyphae formation without affecting human cells to afford sufficient safety. The newly designed 5-[3-substitued-4-(4-substituedbenzyloxy)-benzylidene]-2-thioxo-thiazolidin-4-one derivatives, named SR, showed very specific and effective inhibition activity against C. albicans hyphae formation. SR compounds caused hyphae inhibition activity at concentrations 10-40 fold lower than the concentration required to inhibit Candida yeast and bacterial growths. The anti-hyphae inhibition activities of SR compounds were via activation of the hyphae transcription repressor gene, TUP1. Correlation studies between the expression of TUP1 gene and the activity of SR compounds confirmed that the anti-C. albicans activities of SR compounds were via inhibition of hyphae formation. The newly designed SR compounds showed 10-40% haemolytic activity on human erythrocytes when compared to 100% haemolysis by 0.1% triton employed as positive control. Furthermore, theoretical prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of SR compounds confirmed their safety, efficient metabolism and possible oral bioavailability. With the minimal toxicity and significant activity of the newly-designed SR compounds, a future optimization of pharmaceutical formulation may develop a promising inhibitor of hyphal formation not only for C. albicans but also for other TUP1- dependent dimorphic fungal infections.