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against T. brucei brucei in the submicromolar range of
concentration and are almost not cytotoxic. Due to
the limited number of compounds in the series tested it
is difficult to decide whether mono- or bisnaphthali-
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Such a drug discovery approach was recently called ‘pig-
gy-back’ strategy22 which is useful when a molecular tar-
get in parasites is being pursued for other indications as it
facilitates the identification of chemical starting points. It
has to be noted that structure–activity relationships
emerging from the parasite assays are unlikely to be the
same as observed for the original indications, that is, anti-
tumoral activity1 and allosteric modulation of antagonist
binding to the muscarinic receptors13 herein. However,
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New antitrypanosomal compounds are urgently needed
because the chemotherapy currently depends on very
‘old’ drugs that lack adequate efficacy and cause serious
side effects. Besides being highly potent trypanocidal
compounds, an additional advantage of the naphthali-
mide compounds presented herein is the fact that they
can be easily synthesized in two or three steps with high
yields (see Scheme 1), especially if performed in the micro-
wave.23 Thus, the production costs will be low which is of
high importance for drugs against tropical diseases.
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Acknowledgments
15. Nagarajan, M.; Morrell, A.; Antony, S.; Kohlhagen, G.;
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C.; Chaires, J. B.; Hollingshead, M.; Cushman, M.
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17. Ra¨z, B.; Iten, M.; Grether-Buhler, Y.; Kaminsky, R.;
¨
Thanks are due to the Deutsche Forschungsgemeins-
chaft (SFB 630) for financial support and the National
Institute of Health for initial testing of the compounds
for antitumoral activity.
Brun, R. Acta Trop. 1997, 68, 139.
Supplementary data
18. Huber, W.; Koella, J. C. Acta Trop. 1993, 55, 257.
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E.; McKerrow, J. H.; Holzgrabe, U.; Caffrey, C. R.;
Ponte-Sucre, A.; Moll, H.; Stich, A.; Schirmeister, T.
Bioorg. Med. Chem. Lett. 2006, 16, 2753.
Supplementary data associated with this article can be
20. Ahmed, S. A.; Gogal, R. M.; Walsh, J. E. J. Immunol.
Methods 1994, 170, 211.
21. Carrasco, C.; Joubert, A.; Tardy, C.; Maestre, N.; Cacho,
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