Full Description
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.
Contents
Preface ix
Contributors xi
Part I Introduction 1
1. Introduction to Zinc Enzymes as Drug Targets 3
Claudiu T. Supuran and Jean-Yves Winum
Part II Drug Design of Carbonic Anhydrase Inhibitors and Activators 13
2. Carbonic Anhydrases as Drug Targets: General Presentation 15
Claudiu T. Supuran
3. Zinc Binding Functions in the Design of Carbonic Anhydrase Inhibitors 39
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 73
Vincenzo Alterio, Anna Di Fiore, Katia D'Ambrosio, Claudiu T. Supuran, and Giuseppina De Simone
5. Antiglaucoma Carbonic Anhydrase Inhibitors as Ophthalomologic Drugs 139
Francesco Mincione, Andrea Scozzafava, and Claudiu T. Supuran
6. Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs 155
Daniela Vullo, Alessio Innocenti, and Claudiu T. Supuran
7. Drug Design of Carbonic Anhydrase Inhibitors as Anticonvulsant Agents 171
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 193
Silvia Pastorekova, Monika Barathova, Juraj Kopacek, and Jaromir Pastorek
9. Fluorescent- and Spin-Labeled Sulfonamides as Probe for Carbonic Anhydrase IX 223
Alessandro Cecchi, Laura Ciani, Sandra Ristori, and Claudiu T. Supuran
10. Drug Design of Antiobesity Carbonic Anhydrase Inhibitors 241
Giuseppina De Simone and Claudiu T. Supuran
11. Dual Carbonic Anhydrase and Cyclooxygenase-2 Inhibition 255
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 273
Mika Hilvo, Giuseppina De Simone, Claudiu T. Supuran, and Seppo Parkkila
13. Mechanism and Inhibition of the b-Class and c-Class Carbonic Anhydrases 285
James G. Ferry and Claudiu T. Supuran
14. Fungal and Nematode Carbonic Anhydrases: Their Inhibition in Drug Design 301
Rebecca A. Hall and Fritz. A. M€uhlschlegel
15. Crystallographic Studies on Carbonic Anhydrases from Fungal Pathogens for Structure-Assisted Drug Development 323
Uta-Maria Ohndorf, Christine Schlicker, and Clemens Steegborn
16. Malaria Parasite Carbonic Anhydrase and Its Inhibition in the Development of Novel Therapies of Malaria 335
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 359
Isao Nishimori, Hiroaki Takeuchi, and Claudiu T. Supuran
18. QSAR of Carbonic Anhydrase Inhibitors and Their Impact on Drug Design 375
Adriano Martinelli and Tiziano Tuccinardi
19. Selectivity Issues in the Design of CA Inhibitors 399
Claudiu T. Supuran and Jean-Yves Winum
20. Bicarbonate Transport Metabolons 415
Danielle E. Johnson and Joseph R. Casey
21. Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors 439
Marc A. Ilies
22. Drug Design Studies of Carbonic Anhydrase Activators 473
Claudia Temperini, Andrea Scozzafava, and Claudiu T. Supuran
Part III Drug Design of Matrix Metalloproteinase Inhibitors 487
23. Matrix Metalloproteinases: An Overview 489
Hideaki Nagase and Robert Visse
24. MMP Inhibitors Based on Earlier Succinimide Strategies: From Early to New Approaches 519
M. Amélia Santos
25. Drug Design of Sulfonylated MMP Inhibitors 549
Armando Rossello and Elisa Nuti
26. ADAMs and ADAMTs Selective Synthetic Inhibitors 591
Armando Rossello, Elisa Nuti, and Alfonso Maresca
27. QSAR Studies of MMP Inhibitors 647
Tiziano Tuccinardi and Adriano Martinelli
Part IV Drug Design of Bacterial Zinc Protease Inhibitors 673
28. Bacterial Zinc Proteases as Orphan Targets 675
Claudiu T. Supuran
29. Botulinus Toxin, Tetanus Toxin, and Anthrax Lethal Factor Inhibitors 705
Antonio Mastrolorenzo and Claudiu T. Supuran
30. Clostridium histolyticum Collagenase Inhibitors in the Drug Design 721
Claudiu T. Supuran
31. Other Bacterial Zinc Peptidases as Potential Drug Targets 731
Kunihiko Watanabe
Part V Drug Design Studies of other Zinc-containing Enzymes 749
32. Angiotensin Converting Enzyme (ACE) Inhibitors 751
Ana Camara-Artigas, Vicente Jara-Perez, and Montserrat Andujar-Sanchez
33. P-III Metalloproteinase (Leucurolysin-B) from Bothrops leucurus Venom: Isolation and Possible Inhibition 789
Eladio F. Sanchez and Johannes A. Eble
34. CaaX-Protein Prenyltransferase Inhibitors 813
Martin Schlitzer, Regina Ortmann, and Mirko Altenk€amper
35. Histone Deacetylase Inhibitors 859
Paul W. Finn
36. Recent Development of Diagnostic and Therapeutic Agents Targeting Glutamate Carboxypeptidase II (GCPII) 881
Youngjoo Byun, Ronnie C. Mease, Shawn E. Lupold, and Martin G. Pomper
37. Targeting HIV-1 Integrase Zinc Binding Motif 911
Mario Sechi, Mauro Carcelli, Dominga Rogolino, and Nouri Neamati
38. Inhibitors of Histidinol Dehydrogenases as Antibacterial Agents 937
Pascale Joseph, François Turtaut, Stephan K€ohler, and Jean-Yves Winum
39. Dihydroorotase Inhibitors 951
Mihwa Lee, Megan J. Maher, Richard I. Christopherson, and J. Mitchell Guss
40. APOBEC3G: A Promising Antiviral Target 981
Claudiu T. Supuran and Jean-Yves Winum
Index 989
