The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic
acid hybrids are described herein. The structure of the synthesized products was elucidated by a com-
bination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes
forms of
L. (V) panamensis
, which is the most prevalent
Leishmania
species in Colombia, and against
Trypanosoma cruzi,
which is the pathogenic species to humans. Cytotoxicity was evaluated against hu-
man U-937 macrophages. Eight compounds were active against
L. (V) panamensis
(
18
e
23, 26
and
30
) and
eight of them against
T. cruzi
(
19
e
22
,
24
and
28
e
30
) with EC
50
values lower than 40
m
M. Compounds
19
e
22
,
24
and
28
e
30
showed higher activities than benznidazole (BNZ). Esters
19
and
21
were the most
active compounds for both
L. (V) panamensis
and
T. cruzi
with 3.82 and 11.65
m
M and 8.25 and 8.69
m
M,
respectively. Compounds
19
e
22
,
24
and
28
e
30
showed higher activities than benznidazole (BNZ). Most
of the compounds showed antiprotozoal activity and with exception of
18
,
26
and
28
, the remaining
compounds were toxic for mammalian cells, yet they have potential to be considered as candidates for
anti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length of
the alkyl linker with compound
19
, bearing a four-carbon alkyl chain, the most performing hybrid. In
general, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond in
the side chain is not decisive for cytotoxicity and anti-protozoal activity
