Comprehensive Analysis of Parasite Biology. From Metabolism to Drug Discovery. Drug Discovery in Infectious Diseases

  • ID: 3615624
  • Book
  • 576 Pages
  • John Wiley and Sons Ltd
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Written and edited by experts in the field, this book brings together the current state of the art in phenotypic and rational, target–based approaches to drug discovery against pathogenic protozoa. The chapters focus particularly on virtual compounds and high throughput screening, natural products, computer–assisted drug design, structure–based drug design, mechanism of action identification, and pathway modelling. Furthermore, state–of the art "omics" technologies are described and currently studied enzymatic drug targets are discussed. Mathematical, systems biology–based approaches are introduced as new methodologies for dissecting complex aspects of pathogen survival mechanisms and for target identification. In addition, recently developed anti–parasitic agents targeting particular pathways, which serve as lead compounds for further drug development, are presented.
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List of Contributors IX

Foreword XIX

Preface XXIII

Part One Identification and Validation of New Drugs and Targets 1

1 Discovery of theMechanism of Action of Novel Compounds That Target Unicellular Eukaryotic Parasites 3Daniela Begolo and Christine Clayton

2 Antiparasitics fromAlgae 41Stefan Ringgeler and Barbara Kappes

3 Contribution of Natural Products to Drug Discovery in Tropical Diseases 75Frederick Annang, Olga Genilloud , and Francisca Vicente

4 Isoxazolines: A Novel Chemotype Highly Effective on Ectoparasites 105Tina Weber and Paul M. Selzer

5 Trypanosomal Cysteine Peptidases: Target Validation and Drug Design Strategies 121Elany Barbosa da Silva, Glaécia Aparecida do Nascimento Pereira, and Rafaela Salgado Ferreira

6 Potential of Pyrimidine Metabolism for Antitrypanosomal Drug Discovery 147María Valente, Antonio E. Vidal, and Dolores González Pacanowska

7 Phosphatidylcholine and Phosphatidylethanolamine Biosynthesis Pathways in Plasmodium 171Ewelina Guca, Alicia Contet, Henri J. Vial, KaiWengelnik, and Rachel Cerdan

8 Immunophilins as Possible Drug Targets in Apicomplexan Parasites 193Alessandra Bianchin , Anthony J. Chubb, and Angus Bell

9 Targeting the Atg8 Conjugation Pathway for Novel Anti–Apicomplexan Drug Discovery 213Alexia S. Miller and Jürgen Bosch

10 Turnover of Glycosomes in Trypanosomes Perspectives for Drug Discovery 231Ana Brennand, Eva Rico, Melisa Gualdrón–López, and Paul A.M. Michels

11 Glideosome of Apicomplexans as a Drug Target 255Lauren E. Boucher and Jürgen Bosch

12 N–Myristoyltransferase as a Target for Drug Discovery in Malaria 275James A. Brannigan and Anthony J. Wilkinson

Part Two Metabolomics in Drug and Target Discovery 295

13 Methods to InvestigateMetabolic Systems in Trypanosoma 297Maria Fatarova, Florian Bellvert, Edern Cahoreau, Frédéric Bringaud, and Jean–Charles Portais

14 The Role of Metabolomics in Antiparasitic Drug Discovery 321Carlo R. Giannangelo, Katherine M. Ellis, Anna E. Sexton, Daniel Stoessel, and Darren J. Creek

15 The Importance of Targeting Lipid Metabolism in Parasites for Drug Discovery 343Simon A. Young, Matthew D. Roberts, and Terry K. Smith

16 CarbonMetabolism of Plasmodium falciparum 371Marco Biddau and Sylke Müller

Part Three Gene Expression and Its Regulation A Promising Research Area for Drug Discovery 399

17 Epigenetic Gene Regulation: Key to Development and Survival of Malaria Parasites 401Sabine Anne–Kristin Fraschka and Richárd Bártfai

18 Mechanisms Regulating Transcription in Plasmodium falciparum as Targets for Novel Antimalarial Drugs 421Evelien M. Bunnik and Karine G. Le Roch

19 Aminoacyl t–RNA Synthetases as Antimalarial Drug Targets 441Anmol Chandele and Amit Sharma

Part Four Mathematical Approaches to Drug and Target Discovery 455

20 MathematicalModeling and Omic Data Integration to Understand Dynamic Adaptation of Apicomplexan Parasites and Identify Pharmaceutical Targets 457Partho Sen, Henri J. Vial, and Ovidiu Radulescu

21 Understanding Protozoan Parasite Metabolism and Identifying Drug Targets through Constraint–Based Modeling 487Francis Isidore Totanes, Sanu Shameer, David R.Westhead, Fabien Jourdan, and Glenn A. McConkey

22 Attacking Blood–Borne Parasites with Mathematics 513David D. van Niekerk, Gerald Penkler, François du Toit, Jacky L. Snoep, Barbara M. Bakker, and Jurgen R. Haanstra

Index 543

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Sylke Müller
Rachel Cerdan
Ovidiu Radulescu
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