5-(2-hydroxy-5-chlorobenzylidene)thiazolidine-2,4-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 5-(2-hydroxy-5-chlorobenzylidene)thiazolidine-2,4-dione
• 英文别名: 5-[(5-Chloro-2-hydroxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione
• 化学式: C₁₀H₆ClNO₃S
• 分子量: 255.682
• InChiKey: AYPQOTKHGUTJQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 5-氯代水杨醛 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 5-(2-hydroxy-5-chlorobenzylidene)thiazolidine-2,4-dione
  参考文献：
  名称：

  Selective cytotoxic and genotoxic activities of 5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione against NCI-H292 human lung carcinoma cells

  摘要：

  Background: Thiazolidine-2,4-dione ring system is used as a pharmacophore to build various heterocyclic compounds aimed to interact with biological targets. In the present study, benzylidene-2,4-thiazolidinedione derivatives (compounds 2-5) were synthesized and screened against cancer cell lines and the genotoxicity and cytotoxicity of the most active compound (5) was investigated on normal and lung cancer cell line.Methods: For in vitro cytotoxic screening, the MTT assay was used for HL60 and K562 (leukemia), MCF-7 (breast adenocarcinoma), HT29 (colon adenocarcinoma), HEp-2 (cervix carcinoma) and NCI-H292 (lung carcinoma) tumor cell lines and Alamar-blue assay was used for non-tumor cells (PBMC, human peripheral blood mononuclear cells) were used. Cell morphology was visualized after Giemsa-May-Grunwald staining. DNA content, phosphatidylserine externalization and mitochondrial depolarization were measured by flow cytometry. Genotoxicity was assessed by Comet assay.Results: 5-(2-Bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione (5) presented the most potent cytotoxicity, especially against NCI-H292 lung cancer cell line, with IC50 value of 1.26 mu g/mL after 72 h incubation. None of the compounds were cytotoxic to PBMC. After 48 h incubation, externalization of phosphatidylserine, mitochondrial depolarization, internucleosomal DNA fragmentation and morphological alterations consistent with apoptosis were observed in NCI-H292 cells treated with compound (5). In addition, compound (5) also induced genotoxicity in NCI-H292 cells (2.8-fold increase in damage index compared to the negative control), but not in PBMC.Conclusion: Compound 5 presented selective cytotoxic and genotoxic activity against pulmonary carcinoma (NCI-H292 cells). (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.

  DOI：

  10.1016/j.pharep.2017.11.008

文献信息

• Selective cytotoxic and genotoxic activities of 5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione against NCI-H292 human lung carcinoma cells
  作者：Maria do D. Rodrigues、Priscila B.G.S. Santiago、Karla M.R. Marques、Valéria R.A. Pereira、Maria C.A.B. de Castro、Jeanne C.L.L. Cantalice、Teresinha G. da Silva、Mônica L. Adam、Silene C. do Nascimento、Julianna F.C. de Albuquerque、Gardenia C.G. Militao

  DOI：10.1016/j.pharep.2017.11.008

  日期：2018.6

  Background: Thiazolidine-2,4-dione ring system is used as a pharmacophore to build various heterocyclic compounds aimed to interact with biological targets. In the present study, benzylidene-2,4-thiazolidinedione derivatives (compounds 2-5) were synthesized and screened against cancer cell lines and the genotoxicity and cytotoxicity of the most active compound (5) was investigated on normal and lung cancer cell line.Methods: For in vitro cytotoxic screening, the MTT assay was used for HL60 and K562 (leukemia), MCF-7 (breast adenocarcinoma), HT29 (colon adenocarcinoma), HEp-2 (cervix carcinoma) and NCI-H292 (lung carcinoma) tumor cell lines and Alamar-blue assay was used for non-tumor cells (PBMC, human peripheral blood mononuclear cells) were used. Cell morphology was visualized after Giemsa-May-Grunwald staining. DNA content, phosphatidylserine externalization and mitochondrial depolarization were measured by flow cytometry. Genotoxicity was assessed by Comet assay.Results: 5-(2-Bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione (5) presented the most potent cytotoxicity, especially against NCI-H292 lung cancer cell line, with IC50 value of 1.26 mu g/mL after 72 h incubation. None of the compounds were cytotoxic to PBMC. After 48 h incubation, externalization of phosphatidylserine, mitochondrial depolarization, internucleosomal DNA fragmentation and morphological alterations consistent with apoptosis were observed in NCI-H292 cells treated with compound (5). In addition, compound (5) also induced genotoxicity in NCI-H292 cells (2.8-fold increase in damage index compared to the negative control), but not in PBMC.Conclusion: Compound 5 presented selective cytotoxic and genotoxic activity against pulmonary carcinoma (NCI-H292 cells). (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.