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…ENFERMEDAD
DE
CHAGAS

ABSTRACT

The
Present
and
Future
of
Drug
Discovery
for
Chagas
Disease

Chagas
disease,
also
known
as
American
trypanosomiasis,
is
caused
by
infection

with
the
Trypanosoma
cruzi.
The
Pan
American
Health
Organization
(PAHO)

estimates
that
7.7
million
persons
currently
have
T.
cruzi
infection
in
the
21
endemic

countries.
This
disease
can
be
transmitted
to
humans
by
insect
vectors
that
are

found
only
in
the
American
continent,
mainly,
in
rural
areas
with
unhealthy
housing

conditions
where
poverty
is
a
general
concern.
Nifurtimox
and
benznidazole
are
the

only
drugs
used
against
this
disease,
but
sometimes
they
are
not
available.
The

treatment
of
Chagas
disease
with
nifurtimox
or
benznidazole
is
unsatisfactory

because
of
their
limited
efficacy
on
the
prevalent
chronic
stage
of
the
disease
and

their
toxic
side
effects.
It
is,
therefore,
necessary
the
development
of
new
effective

antichagasic
drugs
for
the
suitable
treatment
of
this
disease.
The
development
of

new
drugs
for
Chagas
disease
requires
a
multidisciplinary
approach
involving
diverse

disciplines
such
as
molecular
and
cellular
biology,
chemistry,
bioinformatics,

biochemistry,
pharmacology
and
toxicology.
This
revision
describes
the
different

strategies
used
for
drug
discovery
on
Chagas
disease
treatment.
The
most
classic

strategies
as
the
design
of
analogous,
the
systematic
screening
or
that
one
based
on

the
biological
information,
together
the
most
recent
methods
based
on

chemiinformatics,
are
presented.

Keywords:
Chagas
Disease;
T.
cruzi;
QSAR;
Cheminformatics;
Virtual
screening;

Neural
network;
Docking.

1.
INTRODUCCIÓN

La
enfermedad
de
Chagas,
también
llamada
Tripanosomiasis
Americana
es

una
enfermedad
parasitaria
causada
por
un
protozoo
flagelado
llamado

Trypanosoma
cruzi.
Este
parásito
es
transmitido
a
los
huéspedes
vertebrados
por

un
insecto
hematófago,
el
Triatoma
infestans,
conocido
como
vinchuca
o
chinche.

La
enfermedad
de
Chagas
también
puede
transmitirse
a
través
de
transfusiones
de

sangre,
de
madres
a
hijos
durante
el
embarazo,
o
con
menos
frecuencia,
a
través
de

trasplantes
de
órganos
o
alimentos
contaminados.
El
parásito
se
reproduce
en
los

tejidos
internos
y
causa
problemas
en
el
corazón,
el
esófago,
el
colon
y
el
sistema

nervioso
(1).

Esta
enfermedad
es
una
endemia
parasitaria
que
afecta
a
unos
7,7
millones

de
personas
en
Latinoamérica,
extendiéndose
desde
el
sur
de
los
Estados
Unidos

hasta
Argentina
y
Chile.
No
existe
vacuna
contra
la
enfermedad
de
Chagas
y
las

personas
afectadas
pueden
volverse
a
infectar
después
de
recibir
tratamiento

farmacológico
(2).

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