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ZFIN ID: ZDB-PUB-150923-4
Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model
Sittaramane, V., Padgett, J., Salter, P., Williams, A., Luke, S., McCall, R., Arambula, J.F., Graves, V.B., Blocker, M., Van Leuven, D., Bowe, K., Heimberger, J., Cade, H.C., Immaneni, S., Shaikh, A.
Date: 2015
Source: ChemMedChem   10(11): 1802-7 (Journal)
Registered Authors: Sittaramane, Vinoth
Keywords: anticancer activity, cytotoxicity, organofluorine compounds, synthesis design, zebrafish
MeSH Terms:
  • Alcohols/chemical synthesis
  • Alcohols/chemistry
  • Alcohols/pharmacology*
  • Alcohols/toxicity
  • Animals
  • Antineoplastic Agents/chemical synthesis
  • Antineoplastic Agents/chemistry
  • Antineoplastic Agents/pharmacology*
  • Antineoplastic Agents/toxicity
  • Cell Death/drug effects
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Hydrocarbons, Fluorinated/chemical synthesis
  • Hydrocarbons, Fluorinated/chemistry
  • Hydrocarbons, Fluorinated/pharmacology*
  • Hydrocarbons, Fluorinated/toxicity
  • Models, Animal
  • Molecular Structure
  • Quinolines/chemistry
  • Quinolines/pharmacology*
  • Quinolines/toxicity*
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays
  • Zebrafish/embryology*
PubMed: 26388134 Full text @ ChemMedChem.
In this study the rational design, synthesis, and anticancer activity of quinoline-derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp(3) -CH functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4-trifluoro-3-hydroxy-3-(quinolin-2-ylmethyl)butanoate (1), 2-benzyl-1,1,1-trifluoro-3-(quinolin-2-yl)propan-2-ol (2), and trifluoro-3-(isoquinolin-1-yl)-2-(thiophen-2-yl)propan-2-ol (3). Compounds 2 and 3 were found to be more toxic than compound 1; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2, with an LC50 value of 14.14 μM, has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents.