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

Journal Article · Fri Mar 15 04:00:00 EDT 2019 · Medicinal Chemistry Research (Print)

DOI:https://doi.org/10.1007/S00044-018-02285-2· OSTI ID:22936208

López-Muñoz, Marisol; Gomez-Peña, Jessica Johanna ^[1]; Ocampo-Cardona, Rogelio ^[2]; Jones, Marjorie A.; Haynes, Craig S.; Wallace, Craig ^[3]; Robledo, Sara M. ^[4]

---

1. Universidad de Caldas, Programa de Maestría en Química (Colombia)
2. Universidad de Caldas, Grupo de investigación “Química Teórica y Bioinformática” Department of Chemistry (Colombia)
3. Illinois State University, Department of Chemistry (United States)
4. Universidad de Antioquia, PECET-School of Medicine (Colombia)

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-CH{sub 2}N(CH{sub 3}){sub 2}(CH{sub 2}){sub n}CH = C(Ar{sub 2})]{sup +}I{sup −} (where X=H, Cl or I, n = 2 or 3, and Ar = m-C{sub 6}H{sub 4}CF{sub 3}, p-C{sub 6}H{sub 4}CF{sub 3}, m-C{sub 6}H{sub 4}F, p-C{sub 6}H{sub 4}F or C{sub 6}H{sub 5}) were tested as potential trypanocidal agents and assessed their cytotoxicity on U-937 cells. CF{sub 3}-substituted QASs exhibited LC{sub 50} values in the range of 0.5 to 6.4 μg/mL and trypanocidal EC{sub 50} values between 0.6 and 7.0 μg/mL, while the LC{sub 50} values for F-substituted analogs are between 7.0 and 207 μg/mL and EC{sub 50} 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.

• OSTI ID: 22936208
• Journal Information: Medicinal Chemistry Research (Print), Journal Name: Medicinal Chemistry Research (Print) Journal Issue: 3 Vol. 28; ISSN 1054-2523
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AROMATICS
DRUGS
FLUORINE
IN VITRO
IODINE IONS
THERAPY
TOXICITY
TRYPANOSOMA