thiazolo[5,4-a]acridine-2(3H),11(6H)-dithione | 261758-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: thiazolo[5,4-a]acridine-2(3H),11(6H)-dithione
• 英文别名: 3,6-Dihydro-[1,3]thiazolo[5,4-a]acridine-2,11-dithione
• CAS: 261758-81-0
• 化学式: C₁₄H₈N₂S₃
• 分子量: 300.429
• InChiKey: BDSXDWQRPIJISW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  正溴丁烷 、 thiazolo[5,4-a]acridine-2(3H),11(6H)-dithione 在 氢氧化钾 作用下， 以 丁酮 为溶剂， 反应 20.0h， 以42%的产率得到2-butylthiothiazolo[5,4-a]acridine-11(6H)-thione
  参考文献：
  名称：

  Robin, Maxime; Faure, Robert; Perichaud, Alain, Heterocycles, 2000, vol. 53, # 2, p. 387 - 395

  摘要：

  DOI：
• 作为产物：
  描述：

  2,11-dichlorothiazolo[5,4-a]acridine 在 tetraphosphorus decasulfide 作用下， 生成 thiazolo[5,4-a]acridine-2(3H),11(6H)-dithione
  参考文献：
  名称：

  DNA-damaging activity and mutagenicity of 16 newly synthesized thiazolo[5,4-a]acridine derivatives with high photo-inducible cytotoxicity

  摘要：

  The discovery of the potent anticancer properties of natural alkaloids in the pyrido-thiazolo-acridine series has suggested that thiazolo-acridine derivatives could be of great interest. In a continuous attempt to develop DNA-binding molecules and DNA photo-cleavers, 16 new thiazolo[5,4a]acridines were synthesized and studied for their photo-inducible DNA-intercalative, cytotoxic and mutagenic activities, by use of the DNA methyl-green bioassay, the Alamar Blue (R) viability assay and the Salmonella mutagenicity test using strains TA97a and TA98 with and without metabolic activation and photo-activation. Without photo-activation, one compound showed a DNA-intercalative activity in the DNA major groove while three compounds displayed intercalating properties after photo-activation. In the dark, four molecules possessed cytotoxic activities against a THP 1 acute monocytic leukemia cell line while 15 derivatives displayed photo-inducible cytotoxic activity against this cell line. All compounds were mutagenic in strain TA97a with metabolic activation (+S9mix) and 15 molecules were mutagenic in strain TA98 without activation (-S9mix). Study of the quantitative structure-activity relationships (QSAR) from the Salmonella mutagenicity data revealed that several descriptors could describe cytotoxic and mutagenic activities after photo-activation. From the results of the mutagenicity test, four compounds with elevated mutagenic activities were selected for additional experiments. Their, capacities to induce single-strand breaks (SSB) and chromosome-damaging effects were monitored by the comet and the micronucleus assays in normal human keratinocytes. Comparison of the minimal genotoxic concentrations showed that two compounds possessed higher capacities to induce SSB after photo-activation. In the micronucleus assay, three molecules were able to induce high numbers of micronuclei following photo-activation. Overall, the results of this study confirm that acridines are predominantly genotoxic via a DNA-intercalating mechanism in the dark, while DNA-adducts were probably induced following photo-activation. (C) 2007 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.mrgentox.2007.10.022

文献信息

• DNA-damaging activity and mutagenicity of 16 newly synthesized thiazolo[5,4-a]acridine derivatives with high photo-inducible cytotoxicity
  作者：Carole Di Giorgio、Anna Nikoyan、Laetitia Decome、Céline Botta、Maxime Robin、Jean-Pierre Reboul、Anne-Sophie Sabatier、Alain Matta、Michel De Méo

  DOI：10.1016/j.mrgentox.2007.10.022

  日期：2008.2

  The discovery of the potent anticancer properties of natural alkaloids in the pyrido-thiazolo-acridine series has suggested that thiazolo-acridine derivatives could be of great interest. In a continuous attempt to develop DNA-binding molecules and DNA photo-cleavers, 16 new thiazolo[5,4a]acridines were synthesized and studied for their photo-inducible DNA-intercalative, cytotoxic and mutagenic activities, by use of the DNA methyl-green bioassay, the Alamar Blue (R) viability assay and the Salmonella mutagenicity test using strains TA97a and TA98 with and without metabolic activation and photo-activation. Without photo-activation, one compound showed a DNA-intercalative activity in the DNA major groove while three compounds displayed intercalating properties after photo-activation. In the dark, four molecules possessed cytotoxic activities against a THP 1 acute monocytic leukemia cell line while 15 derivatives displayed photo-inducible cytotoxic activity against this cell line. All compounds were mutagenic in strain TA97a with metabolic activation (+S9mix) and 15 molecules were mutagenic in strain TA98 without activation (-S9mix). Study of the quantitative structure-activity relationships (QSAR) from the Salmonella mutagenicity data revealed that several descriptors could describe cytotoxic and mutagenic activities after photo-activation. From the results of the mutagenicity test, four compounds with elevated mutagenic activities were selected for additional experiments. Their, capacities to induce single-strand breaks (SSB) and chromosome-damaging effects were monitored by the comet and the micronucleus assays in normal human keratinocytes. Comparison of the minimal genotoxic concentrations showed that two compounds possessed higher capacities to induce SSB after photo-activation. In the micronucleus assay, three molecules were able to induce high numbers of micronuclei following photo-activation. Overall, the results of this study confirm that acridines are predominantly genotoxic via a DNA-intercalating mechanism in the dark, while DNA-adducts were probably induced following photo-activation. (C) 2007 Elsevier B.V. All rights reserved.
• Robin, Maxime; Faure, Robert; Perichaud, Alain, Heterocycles, 2000, vol. 53, # 2, p. 387 - 395
  作者：Robin, Maxime、Faure, Robert、Perichaud, Alain、Galy, Jean-Pierre

  DOI：——

  日期：——