Antiparasitic and antibacterial drug discovery : from molecular targets to drug candidates

Mainly addressing parasitic diseases but also focusing on diseases caused by bacteria, this much-needed reference and handbook provides a unique insight into the approach adopted by commercial science towards infectious diseases, including the work of medicinal chemists. Many of the authors are scientists with hands-on experience of drug discovery units within the pharmaceutical industry. In addition, the text covers efforts towards drug development in infectious diseases from academic groups and non profit organizations.Content: Chapter 1 Target Identification and Mechanism?Based Screening for Anthelmintics: Application of Veterinary Antiparasitic Research Programs to Search for New Antiparasitic Drugs for Human Indications (pages 1–15): Timothy G. Geary, Debra J. Woods, Tracey Williams and Solomon NwakaChapter 2 Anthelmintic Resistance as a Guide to the Discovery of New Drugs? (pages 17–32): Georg v. Samson?Himmelstjerna, Roger K. Prichard and Adrian J. WolstenholmeChapter 3 Drug Discovery for Neglected Diseases: View of A Public–Private Partnership (pages 33–43): Rob Don and Eric ChatelainChapter 4 Bioinformatics and Chemoinformatics: Key Technologies in the Drug Discovery Process (pages 45–57): Andreas Krasky, Andreas Rohwer, Richard J. Marhofer and Prof. Dr. Paul M. SelzerChapter 5 Target Identification and Validation in Antiparasitic Drug Discovery (pages 59–73): Christian Wolf and Nikolas GunkelChapter 6 Selective Drug Targets in Parasites (pages 75–98): Peter Kohler and Richard J. MarhoferChapter 7 Lessons Learned from Target?Based Lead Discovery (pages 99–115): Michael Gassel, Jorg Cramer, Christopher Kern, Sandra Noack and Wolfgang StreberChapter 8 Approaches towards Antiparasitic Drug Candidates for Veterinary Use (pages 117–133): Christophe Chassaing and Harald SekljicChapter 9 Learning to Relate Structural Space to Property Space (pages 135–158): Michael Berger, Jorg Cramer, Michael Hinz, Christina Mertens, Christian Miculka, Trevor Newton, Jorg Schroder and Harald SekljicChapter 10 Recruiting the Host Defense Mechanisms: Roles for Vaccines and Chemotherapeutics (pages 159–173): Theo P. M. SchettersChapter 11 Proteases of Parasitic Protozoa – Current Status and Validation (pages 175–209): Mohammed Sajid, Michael J. Blackman, Patricia Doyle, Chen He, Kirkwood M. Land, Cheryl Lobo, Zachary Mackey, Momar Ndao, Sharon L. Reed, Brian Shiels, Ryan Swenerton and William WeirChapter 12 In Search of Trypanocidal Drugs (pages 211–226): Leopold FloheChapter 13 Trypanosomatid Protein Kinases as Potential Drug Targets (pages 227–247): Martin Wiese, Andrew Morris and Karen M. GrantChapter 14 Targeting the Malaria Kinome: Discovering Kinase Inhibitors as Novel Antimalarial Agents (pages 249–276): Dayadevi Jirage, Susan M. Keenan and Norman C. WatersChapter 15 Malaria and Antimalarials – A Focused View (pages 277–298): Frank SeeberChapter 16 Chemotherapeutic Development Strategies for Schistosomiasis (pages 299–321): Conor R. Caffrey, David L. Williams, Matthew H. Todd, David L. Nelson, Jennifer Keiser and Jurg UtzingerChapter 17 Searching New Antiparasitics in Virtual Space (pages 323–338): Frank Oellien, Kristin Engels, Jorg Cramer, Richard J. Marhofer, Christopher Kern and Prof. Dr. Paul M. SelzerChapter 18 Cyclooctadepsipeptides – An Anthelmintically Active Class of Compounds Exhibiting a Novel Mode of Action (pages 339–356): Achim Harder, Kathryn Bull, Marcus Guest, Lindy Holden?Dye and Robert WalkerChapter 19 Chemical Optimization of Anthelmintic Compounds – A Case Study (pages 357–371): Thorsten Meyer, Jorg Schroder, Manfred Uphoff, Sandra Noack, Anja R. Heckeroth, Michael Gassel, Petra Rohrwild and Thomas IlgChapter 20 Pathogenomics: Identification of Novel Drug Targets and Vaccine Candidates in Bacteria (pages 373–413): Knut Ohlsen, Martin Eckart, Ulrich Dobrindt, Heike Bruhn and Jorg HackerChapter 21 Tuberculosis Drug Discovery: Issues, Gaps and the Way Forward (pages 415–440): Veronique Dartois, Franz Joel Leong and Thomas DickChapter 22 Decreasing the Number of Gaps in the Draft Assembly of the Mannheimia Haemolytica M7/2 Genome Sequence (pages 441–451): Hon Q. Tran, Mathias Beig, Volker Spehr, Andreas Rohwer, Gottfried Unden and Prof. Dr. Paul M. SelzerChapter 23 Total Synthesis and Configurational Assignment of Pasteurestin A and B, a Natural Product with Antimicrobial Activity on Pasteurellaceae (pages 453–471): Marion Kogl, Lothar Brecker, Ralf Warrass and Johann Mulzer This Most Recent Volume In The Series On Drug Discovery In Infectious Diseases Focusses On The Use Of Metabolic Analysis Of Protozoic Parasites For Rational Drug Discovery Design. Covering All Classes Of Parasites, This Ready Reference Covers Such Methodologies As Virtual Compound, High Throughput, And Cellular Screening, As Well As Computer-assisted And Structure-based Drug Design, And Pathway Modelling. Furthermore, Several Chapters Focus On The Latest Technologies Increasingly Being Used To Dissect Metabolic Pathways And Cellular Processes, While Enzymatic Drug Targets For Which Structural, Knock Out And Inhibitor Data Are Available Are Also Included As Well As Recent Antiparasitic Agents Targeting Particular Pathways Serving As Lead Compounds For Further Drug Development. With Its Real-life Success Stories, This Is A Must-have For All Professionals Dealing With Drug Discovery In Parasitology. Identification And Validation Of New Drugs And Targets. Discovery Of The Mechanism Of Action Of Novel Compounds That Target Unicellular Eukaryotic Parasites / Daniela Begolo, Christine Clayton -- Antiparasitics From Algae / Stefan Ringgeler, Barbara Kappes -- Contribution Of Natural Products To Drug Discovery In Tropical Diseases / Frederick Annang, Olga Genilloud, Francisca Vicente -- Isoxazolines: A Novel Chemotype Highly Effective On Ectoparasites / Tina Weber, Paul M Selzer -- Trypanosomal Cysteine Peptidases: Target Validation And Drug Design Strategies / Elany Barbosa Silva, Glaecia Aparecida Nascimento Pereira, Rafaela Salgado Ferreira -- Potential Of Pyrimidine Metabolism For Antitrypanosomal Drug Discovery / Maria Valente, Antonio E Vidal, Dolores Gonzalez Pacanowska -- Phosphatidylcholine And Phosphatidylethanolamine Biosynthesis Pathways In Plasmodium / Ewelina Guca, Alicia Contet, Henri J Vial, Kai Wengelnik, Rachel Cerdan --^ Immunophilins As Possible Drug Targets In Apicomplexan Parasites / Alessandra Bianchin, Anthony J Chubb, Angus Bell -- Targeting The Atg8 Conjugation Pathway For Novel Anti-apicomplexan Drug Discovery / Alexia S Miller, Jurgen Bosch -- Turnover Of Glycosomes In Trypanosomes : Perspectives For Drug Discovery / Ana Brennand, Eva Rico, Melisa Gualdron-lopez, Paul Am Michels -- Glideosome Of Apicomplexans As A Drug Target / Lauren E Boucher, Jurgen Bosch -- N-myristoyltransferase As A Target For Drug Discovery In Malaria / James A Brannigan, Anthony J Wilkinson -- Metabolomics In Drug And Target Discovery. Methods To Investigate Metabolic Systems In Trypanosoma / Maria Fatarova, Florian Bellvert, Edern Cahoreau, Frederic Bringaud, Jean-charles Portais -- The Role Of Metabolomics In Antiparasitic Drug Discovery / Carlo R Giannangelo, Katherine M Ellis, Anna E Sexton, Daniel Stoessel, Darren J Creek --^ The Importance Of Targeting Lipid Metabolism In Parasites For Drug Discovery / Simon A Young, Matthew D Roberts, Terry K Smith -- Carbon Metabolism Of Plasmodium Falciparum / Marco Biddau, Sylke Muller -- Gene Expression And Its Regulation : A Promising Research Area For Drug Discovery. Epigenetic Gene Regulation: Key To Development And Survival Of Malaria Parasites / Sabine Anne-kristin Fraschka, Richard Bartfai -- Mechanisms Regulating Transcription In Plasmodium Falciparum As Targets For Novel Antimalarial Drugs / Evelien M Bunnik, Karine G Le Roch -- Aminoacyl T-rna Synthetases As Antimalarial Drug Targets / Anmol Chandele, Amit Sharma -- Mathematical Approaches To Drug And Target Discovery. Mathematical Modeling And Omic Data Integration To Understand Dynamic Adaptation Of Apicomplexan Parasites And Identify Pharmaceutical Targets / Partho Sen, Henri J Vial, Ovidiu Radulescu --^ Understanding Protozoan Parasite Metabolism And Identifying Drug Targets Through Constraint-based Modeling / Francis Isidore Totanes, Sanu Shameer, David R Westhead, Fabien Jourdan, Glenn A Mcconkey -- Attacking Blood-borne Parasites With Mathematics / David D Niekerk, Gerald Penkler, Francois Toit, Jacky L Snoep, Barbara M Bakker, Jurgen R Haanstra. Edited By Sylke Müller, Rachel Cerdan, And Ovidiu Radulescu. Includes Bibliographical References And Index. Mode Of Access: World Wide Web. Content: Cover -- Foreword -- Contents -- Preface -- List of Contributors -- Part One: Drug Discovery Approaches -- 1 Target Identification and Mechanism-Based Screening for Anthelmintics: Application of Veterinary Antiparasitic Research Programs to Search for New Antiparasitic Drugs for Human Indications -- 2 Anthelmintic Resistance as a Guide to the Discovery of New Drugs? -- 3 Drug Discovery for Neglected Diseases: View of A PublicPrivate Partnership -- 4 Bioinformatics and Chemoinformatics: Key Technologies in the Drug Discovery Process -- 5 Target Identification and Validation in Antiparasitic Drug Discovery -- 6 Selective Drug Targets in Parasites -- 7 Lessons Learned from Target-Based Lead Discovery -- 8 Approaches Towards Antiparasitic Drug Candidates for Veterinary Use -- 9 Learning to Relate Structural Space to Property Space -- 10 Recruiting the Host Defense Mechanisms: Roles for Vaccines and Chemotherapeutics -- Part Two: Protozoan Parasites -- 11 Proteases of Parasitic Protozoa Current Status and Validation -- 12 In Search of Trypanocidal Drugs -- 13 Trypanosomatid Protein Kinases As Potential Drug Targets -- 14 Targeting the Malaria Kinome: Discovering Kinase Inhibitors as Novel Antimalarial Agents -- 15 Malaria and Antimalarials a Focused View -- Part Three: Multicellular Parasites -- 16 Chemotherapeutic Development Strategies for Schistosomiasis -- 17 Searching New Antiparasitics in Virtual Space -- 18 Cyclooctadepsipeptides an Anthelmintically Active Class of Compounds Exhibiting a Novel Mode of Action -- 19 Chemical Optimization of Anthelmintic Compounds A Case Study -- Part Four: Bacteria -- 20 Pathogenomics: Identification of Novel Drug Targets and Vaccine Candidates in Bacteria -- 21 Tuberculosis Drug Discovery: Issues, Gaps and the Way Forward -- 22 Decreasing the Number of Gaps in the Draft Assembly of the Mannheimia haemolytica M7/2 Genome Sequence -- 23 Total Synthesis and Configurational Assignment of Pasteurestin A and B, a Natural Product with Antimicrobial Activity on Pasteurellaceae -- Index. 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. " ... An interesting book that leads the reader through what factors can influence drug discovery and then gives specific examples on the current situation in development of drugs for particular parasitic and bacterial diseases."--ChemMedChem, 2009Addressing parasitic diseases and those caused by bacteria, this much needed reference and handbook provides a unique insight into the approach adopted by commercial science towards infectious diseases, including the work of medicinal chemists. Many of the authors are scientists with hands-on experience of drug discovery units within the pharmaceutical Addressing parasitic diseases and those caused by bacteria, this much needed reference and handbook provides a unique insight into the approach adopted by commercial science towards infectious diseases, including the work of medicinal chemists. Many of the authors are scientists with hands-on experience of drug discovery units within the pharmaceutical industry. In addition, the text covers efforts towards drug development in infectious diseases from academic groups and non profit organizations Addressing parasitic diseases and diseases caused by bacteria, this much-needed reference and handbook provides a unique insight into the approach adopted by academic and commercial science towards infectious diseases, including the work of medicinal chem