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Novel fluorinated quaternary ammonium salts and their in vitro activity as trypanocidal agents

  • Marisol López-Muñoz
  • Jessica Johanna Gomez-Peña
  • Luz Amalia Ríos-VásquezEmail author
  • Rogelio Ocampo-Cardona
  • Marjorie A. Jones
  • Craig S. Haynes
  • Craig Wallace
  • Sara M. Robledo
Original Research
  • 29 Downloads

Abstract

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.

Keywords

Trifluoromethylated quaternary ammonium salts Fluorinated quaternary ammonium salts Trypanosoma cruzi Cytotoxicity Anti-trypanosomal activity 

Notes

Acknowledgements

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2285_MOESM1_ESM.pdf (14.4 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Marisol López-Muñoz
    • 1
  • Jessica Johanna Gomez-Peña
    • 1
  • Luz Amalia Ríos-Vásquez
    • 2
    Email author return OK on get
  • Rogelio Ocampo-Cardona
    • 2
  • Marjorie A. Jones
    • 3
  • Craig S. Haynes
    • 3
  • Craig Wallace
    • 3
  • Sara M. Robledo
    • 4
  1. 1.Programa de Maestría en QuímicaUniversidad de CaldasManizalesColombia
  2. 2.Grupo de investigación “Química Teórica y Bioinformática” Department of ChemistryUniversidad de CaldasManizalesColombia
  3. 3.Department of ChemistryIllinois State UniversityIllinoisUSA
  4. 4.PECET-School of MedicineUniversidad de AntioquiaMedellínColombia

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