New Approaches for the Identification of Drug Targets in Protozoan Parasites - International Review of Cell and Molecular Biology - page 357

CHAPTER SEVEN

New Approaches for the
Identification of Drug Targets
in Protozoan Parasites

Joachim Müller 1 , Andrew Hemphill
Institute of Parasitology, University of Berne, Länggass-Strasse 122, Berne, Switzerland
1 Corresponding author: E-mail: [e-mail]

Contents
1. Introduction

360

2. StrategiesforDrugTargetIdentiication 362

2.1. EvaluationofDrugEfectiveness 362

2.1.1. Screening Systems 362

2.1.2. Quantification of Drug Effectiveness 367

2.2. VisualizationofDrugEfectsonCellularMorphologyandUltrastructure 368

2.3. IdentiicationbyDrug-TargetAinity 370

2.4. IdentiicationofDrugTargetsbyAnalysisofResistantParasites 371

2.5. IdentiicationofDrugTargetsbyGenomeMining 371

2.6. ValidationofDrugTargets 372

3. KindsofDrugTargets 372

3.1. DrugTargetsintheGene-ExpressionMachinery 372

3.1.1. DNA Intercalating Agents 372

3.1.2. DNA Modifying Enzymes 373

3.1.3. Transcriptional Activation or Silencing of Gene Expression as a Target 374

3.1.4. Translation 375

3.2. CytoskeletalProteinsasDrugTargets 376

3.3. DrugTargetsinIntracellularSignaling 377

3.3.1. cAMP-Dependent Pathways 377

3.3.2. Isoflavones and Receptor Kinases 378

3.3.3. Calcium-Dependent Protein Kinases in Apicomplexan Parasites 379

3.4. MembraneIntegrityasaDrugTarget 380

3.5. DrugTargetsinIntermediaryMetabolism 381

3.5.1. Glucose Metabolism 381

3.5.2. Prokaryote-like Pathways in Apicomplexa 382

3.5.3. Nitro Compounds Effective against Microaerophilic or Anaerobic Parasites 383

3.5.4. Nitro Compounds Effective against Aerobic Parasites 384

3.5.5. Radical Formation in Aerobic Parasites 385

3.5.6. The Purine Salvage Pathway 385