New Approaches for the Identification of Drug Targets in Protozoan Parasites - International Review of Cell and Molecular Biology - page 388

The most promising situation for antiparasitic drug development is given
when the drug target is localized in an organelle that is absent from the host
cell. For apicomplexan parasites, the prokaryote-like gene expression system
of the apicoplast provides highly interesting targets for antibiotics bind-
ing to DNA or ribosomal RNA. The tetracycline derivative doxycycline
and the lincosamide clindamycin are, for instance, effective as antimalarials.
These antibiotics may constitute interesting candidates for anti-apicom-
plexan drug development and will deserve further attention.
There is more and more evidence that compounds acting on ubiquitous
targets such as intercalating agents, histone-modifying enzymes, compounds
generating free radicals, and others will provide the basis for the development
of highly efficient drugs with a large therapeutic window. The reason for this
specificity is unknown and provides an interesting field for further investiga-
tions. Moreover, the case studies reported above have shown that many drugs
will not only act on one target, and several drug targets can be identified for
a given compound, depending on the approaches used. Action on multiple
targets is, perhaps, even a prerequisite for a high efficacy of antiparasitic drugs,
e.g. via a simultaneous inhibition of vital parasite functions and induction of
apoptosis of host cells in the vicinity of the parasite. In addition, this would
also slow down resistance formation. If this is the case, the target-based drug
development paradigm ( Sams-Dodd, 2005 ) will be even more questionable
in the case of antiparasitic drugs, and development based on physiological
screenings as shown by Rottmann et al. (2010) will prevail.
ACKNOWLEDGMENTS
The authors acknowledge the financial support of the Swiss National Science Foundation
(grant No. 31-127374 & 3100AO-111780), the Swiss Life Jubilâumsstiftung, Stiftung
Helvetia Sana, and the Gottfried and Julia Bangerter-Rhyner Stiftung. JM was supported by
a fellowship from Novartis (Switzerland)
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