Antiprotozoal activity and DNA binding of dicationic acridones

Montalvo-Quirós, Sandra and Taladriz-Sender, Andrea and Kaiser, Marcel and Dardonville, Christophe. (2015) Antiprotozoal activity and DNA binding of dicationic acridones. Journal of medicinal chemistry, 58 (4). pp. 1940-1949.

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Official URL: http://edoc.unibas.ch/dok/A6357881

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Dicationic acridone derivatives were synthesized and their antiparasitic activity was evaluated. Acridones displayed in vitro nanomolar IC50 values against Trypanosoma brucei rhodesiense STIB900 with selectivity indices <1000. Compounds 1b, 3a, and 3b were as potent as the reference drug melarsoprol in this assay. Submicromolar-range activities were observed against wild-type (NF54) and resistant (K1) strains of Plasmodium falciparum, whereas no significant activity was detected against Trypanosoma cruzi or Leishmania donovani. Compounds 1a and 1b were curative in the STIB900 mouse model for human African trypanosomiasis. UV spectrophotometric titrations and circular dichroism (CD) experiments with fish sperm (FS) DNA showed that these compounds form complexes with DNA with binding affinities in the 10(4) M(-1) range. Biological and biophysical data show that antiparasitic activity, toxicity, and DNA binding of this series of acridones are dependent on the relative position of both imidazolinium cations on the heterocyclic scaffold.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Dec 2017 10:47
Deposited On:10 Apr 2015 09:13

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