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Drug Design of Zinc-Enzyme Inhibitors: Functional, Structural, and Disease Applications

Claudiu T. Supuran (Editor), Jean-Yves Winum (Editor), Binghe Wang (Series Editor)
ISBN: 978-0-470-50815-2
912 pages
October 2009
Drug Design of Zinc-Enzyme Inhibitors: Functional, Structural, and Disease Applications (0470508159) cover image
Brings together functional and structural informationrelevant to the design of drugs targeting zinc enzymes

The second most abundant transition element in living organisms, zinc spans all areas of metabolism, with zinc-containing proteins offering both established and potential drug targets. Drug Design of Zinc-Enzyme Inhibitors brings together functional and structural information relevant to these zinc-containing targets. With up-to-date overviews of the latest developments field, this unique and comprehensive text enables readers to understand zinc enzymes and evaluate them in a drug design context.

With contributions from the leaders of today's research, Drug Design of Zinc-Enzyme Inhibitors covers such key topics as:

  • Major drug targets like carbonic anhydrases, matrix metalloproteinases, bacterial proteases, angiotensin-converting enzyme, histone deacetylase, and APOBEC3G

  • Roles of recently discovered zinc-containing isozymes in cancer, obesity, epilepsy, pain management, malaria, and other conditions

  • Cross reactivity of zinc-enzyme inhibitors and activators

  • The extensive use of X-ray crystallography and QSAR studies for understanding zinc-containing proteins

  • Clinical applications

An essential resource for the discovery and development of new drug molecules, Drug Design of Zinc-Enzyme Inhibitors gives researchers, professionals, students, and academics the foundation to understand and work with zinc enzyme inhibitors and activators.

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PREFACE.

CONTRIBUTORS.

PART I: INTRODUCTION.

1. Introduction to Zinc Enzymes as Drug Targets (Claudiu T. Supuran and Jean-Yves Winum).

PART II: DRUG DESIGN OF CARBONIC ANHYDRASE INHIBITORS AND ACTIVATORS.

2. Carbonic Anhydrases as Drug Targets: General Presentation (Claudiu T. Supuran).

3. Zinc Binding Functions in the Design of Carbonic Anhydrase Inhibitors (Jean-Yves Winum, Jean-Louis Montero, Andrea Scozzafava, and Claudiu T. Supuran).

4. X-Ray Crystallography of Carbonic Anhydrase Inhibitors and Its Importance in Drug Design (Vincenzo Alterio, Anna Di Fiore, Katia D’Ambrosio, Claudiu T. Supuran, and Giuseppina De Simone).

5. Antiglaucoma Carbonic Anhydrase Inhibitors as Ophthalomologic Drugs (Francesco Mincione, Andrea Scozzafava, and Claudiu T. Supuran).

6. Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs (Daniela Vullo, Alessio Innocenti, and Claudiu T. Supuran).

7. Drug Design of Carbonic Anhydrase Inhibitors as Anticonvulsant Agents (Anne Thiry, Jean-Michel Dogne, Claudiu T. Supuran, and Bernard Masereel).

8. Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII (Silvia Pastorekova, Monika Barathova, Juraj Kopacek, and Jaromir Pastorek).

9. Fluorescent- and Spin-Labeled Sulfonamides as Probe for Carbonic Anhydrase IX (Alessandro Cecchi, Laura Ciani, Sandra Ristori, and Claudiu T. Supuran).

10. Drug Design of Antiobesity Carbonic Anhydrase Inhibitors (Giuseppina De Simone and Claudiu T. Supuran).

11. Dual Carbonic Anhydrase and Cyclooxygenase-2 Inhibition (Jean-Michel Dogne, Anne Thiry, Bernard Masereel, and Claudiu T. Supuran).

12. Advances in the Inhibitory and Structural Investigations on Carbonic Anhydrase Isozymes XIII and XV (Mika Hilvo, Giuseppina De Simone, Claudiu T. Supuran, and Seppo Parkkila).

13. Mechanism and Inhibition of the b-Class and c-Class Carbonic Anhydrases (James G. Ferry and Claudiu T. Supuran).

14. Fungal and Nematode Carbonic Anhydrases: Their Inhibition in Drug Design (Rebecca A. Hall and Fritz. A. M€uhlschlegel).

15. Crystallographic Studies on Carbonic Anhydrases from Fungal Pathogens for Structure-Assisted Drug Development (Uta-Maria Ohndorf, Christine Schlicker, and Clemens Steegborn).

16. Malaria Parasite Carbonic Anhydrase and Its Inhibition in the Development of Novel Therapies of Malaria (Jerapan Krungkrai, Sudaratana R. Krungkrai, and Claudiu T. Supuran).

17. Inhibitors of Helicobacter pylori a- and b-Carbonic Anhydrases as Novel Drugs for Gastroduodenal Diseases (Isao Nishimori, Hiroaki Takeuchi, and Claudiu T. Supuran).

18. QSAR of Carbonic Anhydrase Inhibitors and Their Impact on Drug Design (Adriano Martinelli and Tiziano Tuccinardi).

19. Selectivity Issues in the Design of CA Inhibitors (Claudiu T. Supuran and Jean-Yves Winum).

20. Bicarbonate Transport Metabolons (Danielle E. Johnson and Joseph R. Casey).

21. Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors (Marc A. Ilies).

22. Drug Design Studies of Carbonic Anhydrase Activators (Claudia Temperini, Andrea Scozzafava, and Claudiu T. Supuran).

PART III DRUG DESIGN OF MATRIX METALLOPROTEINASE INHIBITORS.

23. Matrix Metalloproteinases: An Overview (Hideaki Nagase and Robert Visse).

24. MMP Inhibitors Based on Earlier Succinimide Strategies: From Early to New Approaches (M. Amelia Santos).

25. Drug Design of Sulfonylated MMP Inhibitors (Armando Rossello and Elisa Nuti).

26. ADAMs and ADAMTs Selective Synthetic Inhibitors (Armando Rossello, Elisa Nuti, and Alfonso Maresca).

27. QSAR Studies of MMP Inhibitors (Tiziano Tuccinardi and Adriano Martinelli).

PART IV DRUG DESIGN OF BACTERIAL ZINC PROTEASE INHIBITORS.

28. Bacterial Zinc Proteases as Orphan Targets (Claudiu T. Supuran).

29. Botulinus Toxin, Tetanus Toxin, and Anthrax Lethal Factor Inhibitors (Antonio Mastrolorenzo and Claudiu T. Supuran).

30. Clostridium histolyticum Collagenase Inhibitors in the Drug Design (Claudiu T. Supuran).

31. Other Bacterial Zinc Peptidases as Potential Drug Targets (Kunihiko Watanabe).

PART V DRUG DESIGN STUDIES OF OTHER ZINC-CONTAINING ENZYMES.

32. Angiotensin Converting Enzyme (ACE) Inhibitors (Ana Camara-Artigas, Vicente Jara-Perez, and Montserrat Andujar-Sanchez).

33. P-III Metalloproteinase (Leucurolysin-B) from Bothrops leucurus Venom: Isolation and Possible Inhibition (Eladio F. Sanchez and Johannes A. Eble).

34. CaaX-Protein Prenyltransferase Inhibitors (Martin Schlitzer, Regina Ortmann, and Mirko Altenkamper).

35. Histone Deacetylase Inhibitors (Paul W. Finn).

36. Recent Development of Diagnostic and Therapeutic Agents Targeting Glutamate Carboxypeptidase II (GCPII) (Youngjoo Byun, Ronnie C. Mease, Shawn E. Lupold, and Martin G. Pomper).

37. Targeting HIV-1 Integrase Zinc Binding Motif (Mario Sechi, Mauro Carcelli, Dominga Rogolino, and Nouri Neamati).

38. Inhibitors of Histidinol Dehydrogenases as Antibacterial Agents (Pascale Joseph, Franc¸ois Turtaut, Stephan K€ohler, and Jean-Yves Winum).

39. Dihydroorotase Inhibitors (Mihwa Lee, Megan J. Maher, Richard I. Christopherson, and J. Mitchell Guss).

40. APOBEC3G: A Promising Antiviral Target (Claudiu T. Supuran and Jean-Yves Winum).

Index.

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Claudiu T. Supuran is a professor in the Department of Chemistry at the University of Florence, Italy. His main research interests include medicinal chemistry, design of enzyme inhibitors and activators, X-ray crystallography of metallo-enzymes, and metal complexes with biologically active ligands (metal-based drugs). He has published more than 400 original research papers in these fields.

Jean-Yves Winum is an assistant professor in the Department of Chemistry at the University of Montpellier 2 (Institut des Biomolécules Max Mousseron UMR CNRS 5247), France. His research interests are focused on organic/medicinal chemistry of metallo-enzyme inhibitors and activators.

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