This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tasdemir, D.
Right arrow Articles by Rüedi, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tasdemir, D.
Right arrow Articles by Rüedi, P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2006, p. 1352-1364, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1352-1364.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antitrypanosomal and Antileishmanial Activities of Flavonoids and Their Analogues: In Vitro, In Vivo, Structure-Activity Relationship, and Quantitative Structure-Activity Relationship Studies

Deniz Tasdemir,1* Marcel Kaiser,2 Reto Brun,2 Vanessa Yardley,3 Thomas J. Schmidt,4 Fatma Tosun,5 and Peter Rüedi1

Organisch-Chemisches Institut, Universität Zürich, Zürich, Switzerland,1 Departement Medizinische Parasitologie und Infektionsbiologie, Schweizerisches Tropeninstitut, Basel, Switzerland,2 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom,3 Institut für Pharmazeutische Biologie und Phytochemie, Westfälische Wilhelms-Universität Münster, Münster, Germany,4 Department Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, Turkey5

Received 14 March 2005/ Returned for modification 11 April 2005/ Accepted 8 December 2005

Trypanosomiasis and leishmaniasis are important parasitic diseases affecting millions of people in Africa, Asia, and South America. In a previous study, we identified several flavonoid glycosides as antiprotozoal principles from a Turkish plant. Here we surveyed a large set of flavonoid aglycones and glycosides, as well as a panel of other related compounds of phenolic and phenylpropanoid nature, for their in vitro activities against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani. The cytotoxicities of more than 100 compounds for mammalian L6 cells were also assessed and compared to their antiparasitic activities. Several compounds were investigated in vivo for their antileishmanial and antitrypanosomal efficacies in mouse models. Overall, the best in vitro trypanocidal activity for T. brucei rhodesiense was exerted by 7,8-dihydroxyflavone (50% inhibitory concentration [IC50], 68 ng/ml), followed by 3-hydroxyflavone, rhamnetin, and 7,8,3',4'-tetrahydroxyflavone (IC50s, 0.5 µg/ml) and catechol (IC50, 0.8 µg/ml). The activity against T. cruzi was moderate, and only chrysin dimethylether and 3-hydroxydaidzein had IC50s less than 5.0 µg/ml. The majority of the metabolites tested possessed remarkable leishmanicidal potential. Fisetin, 3-hydroxyflavone, luteolin, and quercetin were the most potent, giving IC50s of 0.6, 0.7, 0.8, and 1.0 µg/ml, respectively. 7,8-Dihydroxyflavone and quercetin appeared to ameliorate parasitic infections in mouse models. Generally, the test compounds lacked cytotoxicity in vitro and in vivo. By screening a large number of flavonoids and analogues, we were able to establish some general trends with respect to the structure-activity relationship, but it was not possible to draw clear and detailed quantitative structure-activity relationships for any of the bioactivities by two different approaches. However, our results can help in directing the rational design of 7,8-dihydroxyflavone and quercetin derivatives as potent and effective antiprotozoal agents.

* Corresponding author. Mailing address: Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. Phone: 41-1-635 42 13. Fax: 41-1-635 68 12. E-mail: deniz{at}oci.unizh.ch.

Antimicrobial Agents and Chemotherapy, April 2006, p. 1352-1364, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1352-1364.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sulsen, V. P., Frank, F. M., Cazorla, S. I., Anesini, C. A., Malchiodi, E. L., Freixa, B., Vila, R., Muschietti, L. V., Martino, V. S. (2008). Trypanocidal and Leishmanicidal Activities of Sesquiterpene Lactones from Ambrosia tenuifolia Sprengel (Asteraceae). Antimicrob. Agents Chemother. 52: 2415-2419 [Abstract] [Full Text]  
  • Sulsen, V. P., Cazorla, S. I., Frank, F. M., Redko, F. C., Anesini, C. A., Coussio, J. D., Malchiodi, E. L., Martino, V. S., Muschietti, L. V. (2007). Trypanocidal and Leishmanicidal Activities of Flavonoids from Argentine Medicinal Plants. Am J Trop Med Hyg 77: 654-659 [Abstract] [Full Text]  
  • Kaiser, M., Wittlin, S., Nehrbass-Stuedli, A., Dong, Y., Wang, X., Hemphill, A., Matile, H., Brun, R., Vennerstrom, J. L. (2007). Peroxide Bond-Dependent Antiplasmodial Specificity of Artemisinin and OZ277 (RBx11160). Antimicrob. Agents Chemother. 51: 2991-2993 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»