Main description:

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.

Contents:

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 3 Daniela Begolo and Christine Clayton 2 Antiparasitics fromAlgae 41 Stefan Ringgeler and Barbara Kappes 3 Contribution of Natural Products to Drug Discovery in Tropical Diseases 75 Frederick Annang, Olga Genilloud , and Francisca Vicente 4 Isoxazolines: A Novel Chemotype Highly Effective on Ectoparasites 105 Tina Weber and Paul M. Selzer 5 Trypanosomal Cysteine Peptidases: Target Validation and Drug Design Strategies 121 Elany Barbosa da Silva, Glaecia Aparecida do Nascimento Pereira, and Rafaela Salgado Ferreira 6 Potential of Pyrimidine Metabolism for Antitrypanosomal Drug Discovery 147 Maria Valente, Antonio E. Vidal, and Dolores Gonzalez Pacanowska 7 Phosphatidylcholine and Phosphatidylethanolamine Biosynthesis Pathways in Plasmodium 171 Ewelina Guca, Alicia Contet, Henri J. Vial, KaiWengelnik, and Rachel Cerdan 8 Immunophilins as Possible Drug Targets in Apicomplexan Parasites 193 Alessandra Bianchin , Anthony J. Chubb, and Angus Bell 9 Targeting the Atg8 Conjugation Pathway for Novel Anti-Apicomplexan Drug Discovery 213 Alexia S. Miller and Jurgen Bosch 10 Turnover of Glycosomes in Trypanosomes Perspectives for Drug Discovery 231 Ana Brennand, Eva Rico, Melisa Gualdron-Lopez, and Paul A.M. Michels 11 Glideosome of Apicomplexans as a Drug Target 255 Lauren E. Boucher and Jurgen Bosch 12 N-Myristoyltransferase as a Target for Drug Discovery in Malaria 275 James A. Brannigan and Anthony J. Wilkinson Part Two Metabolomics in Drug and Target Discovery 295 13 Methods to InvestigateMetabolic Systems in Trypanosoma 297 Maria Fatarova, Florian Bellvert, Edern Cahoreau, Frederic Bringaud, and Jean-Charles Portais 14 The Role of Metabolomics in Antiparasitic Drug Discovery 321 Carlo 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 343 Simon A. Young, Matthew D. Roberts, and Terry K. Smith 16 CarbonMetabolism of Plasmodium falciparum 371 Marco Biddau and Sylke Muller 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 401 Sabine Anne-Kristin Fraschka and Richard Bartfai 18 Mechanisms Regulating Transcription in Plasmodium falciparum as Targets for Novel Antimalarial Drugs 421 Evelien M. Bunnik and Karine G. Le Roch 19 Aminoacyl t-RNA Synthetases as Antimalarial Drug Targets 441 Anmol 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 457 Partho Sen, Henri J. Vial, and Ovidiu Radulescu 21 Understanding Protozoan Parasite Metabolism and Identifying Drug Targets through Constraint-Based Modeling 487 Francis Isidore Totanes, Sanu Shameer, David R.Westhead, Fabien Jourdan, and Glenn A. McConkey 22 Attacking Blood-Borne Parasites with Mathematics 513 David D. van Niekerk, Gerald Penkler, Francois du Toit, Jacky L. Snoep, Barbara M. Bakker, and Jurgen R. Haanstra Index 543