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clindamycin or trimethoprim alone or in combination with sulfonamides
( Greif et al., 2001 ). These drugs are not specific for toxoplasmosis, they do
not notably affect the tissue cyst stage, and may have side effects, mainly in
pregnant women ( Innes and Vermeulen, 2007 ; Petersen et al., 2010 ). These
few examples show that novel and more specific drugs are needed to supple-
ment the arsenal of antiparasitic compounds. In principle, drug development
occurs by two complementary approaches, namely whole organism screening
( Cos et al., 2006 ) and drug target-based development ( Seib et al., 2009 ). In
any case, the drug targets have to be validated in a multistep process ( Egner
et al., 2005 ). The screening for inhibitors derived from natural compounds or
from libraries of de novo synthesized compounds based on existing chemical
scaffolds provides still a major source of drug candidates ( Kayser et al., 2003 ).
Currently, an increasing effort in drug design based on genomics and pro-
teomics is made but it is unclear to which extent it will replace classical drug
screening ( Timmers et al., 2009 ). In order to provide a rationale for the mode
of action of a given compound, in each case, the drug target has to be identi-
fied. Here, we present a review on recent approaches for the identification of
drug targets in protozoan parasites.
2. STRATEGIES FOR DRUG TARGET IDENTIFICATION
2.1. Evaluation of Drug Effectiveness
2.1.1. Screening Systems
The starting point of each whole organism-based screening for antiparasitic
compounds is the setup of a suitable system. Since in vivo tests are expensive
and are limited for ethical reasons, in vitro systems have replaced in vivo
tests as a first step of drug development. A panel of suitable in vitro methods
for antiparasitic drug screening is given in Table 7.2 .
For monitoring the effects on parasite proliferation, morphological
assays represent the gold standard. In the case of axenically grown proto-
zoa (e.g. G. lamblia ), cultures are treated with the compounds to be tested,
and after a given time period, the live parasites are counted under the
microscope ( Müller et al., 2006 ). This provides information not only on
growth inhibition but also on effects on shape and mobility of the para-
site. In the case of obligate biotrophic parasites grown in co-culture with
host cells, parasite-specific structures such as intracellular cysts are visualized
by selected staining methods ( Müller et al., 2009a ) prior to counting. All
 
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