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  • Meeting abstract
  • Open Access

Submitochondrial particles from Saccharomyces cerevisiae to screen compounds for antiprotozoal activity

  • 1,
  • 2,
  • 3 and
  • 1Email author
BMC Pharmacology20077 (Suppl 2) :A56

  • Published:


  • Cell Wall
  • Saccharomyces Cerevisiae
  • Yeast Strain
  • Drug Target
  • Complex Activity

The development of atovaquone (ATQ)-resistant plasmodia strains suggests a need of new drugs for the mitochondrial bc1 complex as drug target in protozoa. It was the aim of the study to establish a model consisting of submitochondrial particles (SMP) from yeast (mimicking the protozoal drug target) and bovine heart for the screening of compounds. Saccharomyces cerevisiae wild-type strains (W303-1A, DBY747) were grown on YPD-media at 30°C for three days. After harvesting the cells their cell wall was digested by zymolyase and mitochondria were isolated. From these organelles SMP where prepared by sonication. The inhibition of the quinol:cyt c oxidoreductase activity catalyzed by the mitochondrial bc1 complex of yeast and bovine heart SMP was measured for a nonspecies-specific inhibitor stigmatellin and for the anti-malaria drug ATQ. IC50 values for stigmatellin in both SMP preparations confirmed its nonselectivity while ATQ inhibited the yeast complex activity about 16 times stronger than the activity of bovine heart SMP. This confirms the functionality of yeast SMP as model for protozoa. A new lead structure TMC2O demonstrated an IC50 value of 808 μM and 112 μM in yeast and bovine heart SMP, respectively. This suggests that structural adjustments are required to increase the inhibition in yeast/protozoa. The yeast model in context with yeast strains mimicking mutated protozoa provides an efficient way to develop drugs for ATQ-resistant plasmodia strains.

Authors’ Affiliations

Department of Natural Sciences, University of Veterinary Medicine, Vienna, Austria
Max F. Perutz Laboratories, University of Vienna, Austria
Department of Chemistry, University of Natural Resources and Applied Life Sciences, Vienna, Austria


© Streicher et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.