Novel fluorinated quaternary ammonium salts and their in vitro activity as trypanocidal agents
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As the impact of aromatic rings and fluorine substituents in commercial drugs is attributed to their electronic distribution and structure rigidity that determine metabolic stability and toxicity, 30 quaternary ammonium salts (QAS) of the form [X-CH2N(CH3)2(CH2)nCH = C(Ar2)]+I− (where X=H, Cl or I, n = 2 or 3, and Ar = m-C6H4CF3, p-C6H4CF3, m-C6H4F, p-C6H4F or C6H5) were tested as potential trypanocidal agents and assessed their cytotoxicity on U-937 cells. CF3-substituted QASs exhibited LC50 values in the range of 0.5 to 6.4 μg/mL and trypanocidal EC50 values between 0.6 and 7.0 μg/mL, while the LC50 values for F-substituted analogs are between 7.0 and 207 μg/mL and EC50 values range from 3.8 to 40.9 μg/mL. As a general trend, the more effective are those bearing an N-iodomethyl moiety or having a longer tether, and para-substituted ones. Few drugs therapies are in use for Chagas disease, so this study becomes a promising contribution.
KeywordsTrifluoromethylated quaternary ammonium salts Fluorinated quaternary ammonium salts Trypanosoma cruzi Cytotoxicity Anti-trypanosomal activity
The authors are grateful to Departamento Administrativo de Ciencia, Tecnología e Innovación - COLCIENCIAS and Universidad de Caldas for the financial support through the Grant No. 112765843017.
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Conflict of interest
The authors declare that they have no conflict of interest.
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