Discovery of Quinoline‐Derived Trifluoromethyl Alcohols,Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model |
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Authors: | Prof. Dr. Vinoth Sittaramane Jihan Padgett Philip Salter Ashley Williams Shauntelle Luke Rebecca McCall Prof. Dr. Jonathan F. Arambula Vincent B. Graves Mark Blocker David Van Leuven Keturah Bowe Julia Heimberger Hannah C. Cade Supriya Immaneni Prof. Dr. Abid Shaikh |
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Affiliation: | 1. Department of Biology, Georgia Southern University, Statesboro, GA, USA;2. Department of Chemistry, Georgia Southern University, Statesboro, GA, USA |
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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 sp3‐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. |
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Keywords: | anticancer activity cytotoxicity organofluorine compounds synthesis design zebrafish |
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