Novel fluorinated quaternary ammonium salts and their in vitro activity as trypanocidal agents
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 2 N(CH 3 ) 2 (CH 2 ) n CH = C(Ar 2 )] + I − (where...
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Published in: | Medicinal chemistry research Vol. 28; no. 3; pp. 300 - 319 |
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Main Authors: | , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
New York
Springer US
15-03-2019
Springer Nature B.V |
Subjects: | |
Online Access: | Get full text |
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Summary: | 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
2
N(CH
3
)
2
(CH
2
)
n
CH = C(Ar
2
)]
+
I
−
(where X=H, Cl or I,
n
= 2 or 3, and Ar =
m
-C
6
H
4
CF
3
,
p
-C
6
H
4
CF
3
,
m
-C
6
H
4
F,
p
-C
6
H
4
F or C
6
H
5
) were tested as potential trypanocidal agents and assessed their cytotoxicity on U-937 cells. CF
3
-substituted QASs exhibited LC
50
values in the range of 0.5 to 6.4 μg/mL and trypanocidal EC
50
values between 0.6 and 7.0 μg/mL, while the LC
50
values for F-substituted analogs are between 7.0 and 207 μg/mL and EC
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. |
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ISSN: | 1054-2523 1554-8120 |
DOI: | 10.1007/s00044-018-02285-2 |