Apicomplexan Parasites - Molecular Approaches Toward Targeted Drug Development

This handbook deals with the discovery of drugs to fight apicomplexan parasites, a group of endoparasites that includes the causative agents of malaria, toxoplasmosis, and babesiosis, among others. Written by renowned scientific experts from academia and industry, the book focuses on current drug development approaches for all apicomplexan diseases, thus making it attractive to a large audience ranging from research labs in academia to the human and veterinarian pharmaceutical industry.

This is the second volume in our exciting book series Drug Discovery in Infectious Diseases, edited by Prof. Paul M. Selzer.

Volume editor:
Katja Becker obtained her degree in medicine from Heidelberg University. She carried out her doctoral thesis as well as her lecturing qualification at the Biochemistry Centre, Heidelberg, before obtaining a Junior Group Leader Position at the Research Center for Infectious Diseases, Würzburg University. She has held the chair for Nutritional Biochemistry at the Justus-Liebig University Giessen since 2000. Her scientific focus is on the characterization of redox active proteins as drug targets, and she has produced more than 170 scientific publications and received numerous scientific awards, including the Carus Medal of the German Academy of Sciences Leopoldina and the Leuckart Medal of the German Society for Parasitology. Professor Becker has been a member of the Leopoldina since June 2009.

Series Editor:
Paul M. Selzer studied biology, parasitology, and biochemistry at the University of Tübingen, Germany, where he also received his PhD in biochemistry. He spent three years in the parasitology and tropical disease laboratory of Prof. James H. McKerrow at the University of California, San Francisco. During his professional career he has worked as a researcher and scientific manager for several pharmaceutical companies, and is currently employed by Intervet Innovation GmbH, Germany, part of a leading animal health company. He is also a visiting professor and teacher in biochemistry, bioinformatics, and chemoinformatics at the University of Tübingen, and an honorary professor of the Department of Infection and Immunity at the University of Glasgow, UK.

Foreword.

Preface.

List of Contributors.

Part One Screening, Bioinformatics, Chemoinformatics, and Drug Design.

1 Drug Discovery Approaches Toward Anti-Parasitic Agents (Andreas Rohwer, Richard J. Marhöfer, Conor R. Caffrey, and Paul M. Selzer).

2 New Bioinformatic Strategies Against Apicomplexan Parasites (Thomas Dandekar and Ke Xiao).

3 Sorting Potential Therapeutic Targets in Apicomplexa (Jan A. Hiss and Gisbert Schneider).

4 Alternatives to Drug Development in the Apicomplexa (Theo P.M. Schetters).

Part Two Metabolic Pathways and Processes Addressed by Current Drug-Discovery Approaches.

5 Energy Metabolism as an Antimalarial Drug Target (Esther Jortzik and Katja Becker).

6 Polyamines in Apicomplexan Parasites (Ingrid B. Müller, Robin Das Gupta, Kai Lüersen, Carsten Wrenger,

and Rolf D. Walter).

7 The Reducing Milieu of Parasitized Cells as a Target of Antimalarial Agents: Methylene Blue as an Ethical Drug (Peter Meissner, Heike Adler, Denis Kasozi, Karin Fritz-Wolf, and R. Heiner Schirmer).

8 Lipids as Drug Targets for Malaria Therapy (Henri J. Vial, Diana Penarete, Sharon Wein, Sergio Caldarelli, Laurent Fraisse, and Suzanne Peyrottes).

9 Targeting Apicoplast Pathways in Plasmodium (Snober S. Mir, Subir Biswas, and Saman Habib).

10 Lipoic Acid Acquisition and Glutathione Biosynthesis in Apicomplexan Parasites (Janet Storm, Eva-Maria Patzewitz, and Sylke Müller).

11 Antimalarial Drugs and Molecules Inhibiting Hemozoin Formation (Uday Bandyopadhyay and Sumanta Dey).

12 Exploiting the Vitamin Metabolism of Apicomplexa as Drug Targets (Carsten Wrenger and Ingrid B. Müller).

13 Vitamin Biosynthetic Pathways, the PLP Synthase Complex, and the Potential for Targeting Protein–Protein Interaction (Ivo Tews and Irmgard Sinning).

14 Targeting Prokaryotic Enzymes in the Eukaryotic Pathogen Cryptosporidium (Suresh Kumar Gorla, Corey Johnson, Jihan Khan, Xin Sun, Lisa Sharling, Boris Striepen, and Lizbeth Hedstrom).

Part Three Drug Targets in Apicomplexan Parasites.

15 Novel Apicomplexan Phosphatases and Immunophilins as Domain-Specific Drug Targets (Sailen Barik).

16 Dehydrogenases and Enzymes of the Mitochondrial Electron Transport Chain as Anti-Apicomplexan Drug Targets (Kathleen Zocher, Stefan Rahlfs, and Katja Becker).

17 Calcium-Dependent Protein Kinases as Drug Targets in Apicomplexan Parasites (Dominik Kugelstadt, Bianca Derrer, and Barbara Kappes).

18 Protein Acylation: New Potential Targets for Intervention Against the Apicomplexa (Joana M. Santos, Christian Hedberg, and Dominique Soldati-Favre).

19 Drugs and Drug Targets in Neospora caninum and Related Apicomplexans (Joachim Müller, Norbert Müller, and Andrew Hemphill).

Part Four Compounds.

20 Subversive Substrates of Glutathione Reductases from Plasmodium falciparum-Infected Red Blood Cells as Antimalarial Agents (Elisabeth Davioud-Charvet and Don Antoine Lanfranchi).

21 Ferroquine: A Concealed Weapon (Christophe Biot, Bruno Pradines, and Daniel Dive).

22 Current Aspects of Endoperoxides in Antiparasitic Chemotherapy (Denis Matovu Kasozi, Stefan Rahlfs, and Katja Becker).

23 Plasmodium Hsp90 as an Antimalarial Target (G. Sridhar Prasad, Nicholas D.P. Cosford, and Sailen Barik).

24 Drug Discovery Against Babesia and Toxoplasma (Mohamad Alaa Terkawi and Ikuo Igarashi).

25 Search for Drugs and Drug Targets against Babesia bovis, Babesia bigemina, Babesia caballi, and Babesia (Theileria) equi (Sabine Bork-Mimm).

26 Orlistat: A Repositioning Opportunity as a Growth Inhibitor of Apicomplexan Parasites? (Christian Miculka, Hon Q. Tran, Thorsten Meyer, Anja R. Heckeroth, Stefan Baumeister, Frank Seeber, and Paul M. Selzer).

27 Recent Drug Discovery Against Cryptosporidium (Jean-François Rossignol, J. Edward Semple, Andrew V. Stachulski, and Gilles Gargala).

Index.