PUBLICATION
Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model
- Authors
- 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.
- ID
- ZDB-PUB-150923-4
- 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.
Citation
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. (2015) Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model. ChemMedChem. 10(11):1802-7.
Abstract
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) -CH 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping