Drug Design of Zinc-Enzyme Inhibitors: Functional, Structural, and Disease Applications (Wiley Series in Drug Discovery and Development)

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. DRUG DESIGN OF ZINC-ENZYME INHIBITORS......Page 4 CONTENTS......Page 8 PREFACE......Page 12 CONTRIBUTORS......Page 14 PART I INTRODUCTION......Page 20 1. Introduction to Zinc Enzymes as Drug Targets......Page 22 PART II DRUG DESIGN OF CARBONIC ANHYDRASE INHIBITORS AND ACTIVATORS......Page 32 2. Carbonic Anhydrases as Drug Targets: General Presentation......Page 34 3. Zinc Binding Functions in the Design of Carbonic Anhydrase Inhibitors......Page 58 4. X-Ray Crystallography of Carbonic Anhydrase Inhibitors and Its Importance in Drug Design......Page 92 5. Antiglaucoma Carbonic Anhydrase Inhibitors as Ophthalomologic Drugs......Page 158 6. Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs......Page 174 7. Drug Design of Carbonic Anhydrase Inhibitors as Anticonvulsant Agents......Page 190 8. Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII......Page 212 9. Fluorescent- and Spin-Labeled Sulfonamides as Probe for Carbonic Anhydrase IX......Page 242 10. Drug Design of Antiobesity Carbonic Anhydrase Inhibitors......Page 260 11. Dual Carbonic Anhydrase and Cyclooxygenase-2 Inhibition......Page 274 12. Advances in the Inhibitory and Structural Investigations on Carbonic Anhydrase Isozymes XIII and XV......Page 292 13. Mechanism and Inhibition of the β-Class and γ-Class Carbonic Anhydrases......Page 304 14. Fungal and Nematode Carbonic Anhydrases: Their Inhibition in Drug Design......Page 320 15. Crystallographic Studies on Carbonic Anhydrases from Fungal Pathogens for Structure-Assisted Drug Development......Page 342 16. Malaria Parasite Carbonic Anhydrase and Its Inhibition in the Development of Novel Therapies of Malaria......Page 354 17. Inhibitors of Helicobacter pylori α- and β-Carbonic Anhydrases as Novel Drugs for Gastroduodenal Diseases......Page 378 18. QSAR of Carbonic Anhydrase Inhibitors and Their Impact on Drug Design......Page 394 19. Selectivity Issues in the Design of CA Inhibitors......Page 418 20. Bicarbonate Transport Metabolons......Page 434 21. Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors......Page 458 22. Drug Design Studies of Carbonic Anhydrase Activators......Page 492 PART III DRUG DESIGN OF MATRIX METALLOPROTEINASE INHIBITORS......Page 506 23. Matrix Metalloproteinases: An Overview......Page 508 24. MMP Inhibitors Based on Earlier Succinimide Strategies: From Early to New Approaches......Page 538 25. Drug Design of Sulfonylated MMP Inhibitors......Page 568 26. ADAMs and ADAMTs Selective Synthetic Inhibitors......Page 610 27. QSAR Studies of MMP Inhibitors......Page 666 PART IV DRUG DESIGN OF BACTERIAL ZINC PROTEASE INHIBITORS......Page 692 28. Bacterial Zinc Proteases as Orphan Targets......Page 694 29. Botulinus Toxin, Tetanus Toxin, and Anthrax Lethal Factor Inhibitors......Page 724 30. Clostridium histolyticum Collagenase Inhibitors in the Drug Design......Page 740 31. Other Bacterial Zinc Peptidases as Potential Drug Targets......Page 750 PART V DRUG DESIGN STUDIES OF OTHER ZINC-CONTAINING ENZYMES......Page 768 32. Angiotensin Converting Enzyme (ACE) Inhibitors......Page 770 33. P-III Metalloproteinase (Leucurolysin-B) from Bothrops leucurus Venom: Isolation and Possible Inhibition......Page 808 34. CaaX-Protein Prenyltransferase Inhibitors......Page 832 35. Histone Deacetylase Inhibitors......Page 878 36. Recent Development of Diagnostic and Therapeutic Agents Targeting Glutamate Carboxypeptidase II (GCPII)......Page 900 37. Targeting HIV-1 Integrase Zinc Binding Motif......Page 930 38. Inhibitors of Histidinol Dehydrogenases as Antibacterial Agents......Page 956 39. Dihydroorotase Inhibitors......Page 970 40. APOBEC3G: A Promising Antiviral Target......Page 1000 Index......Page 1008 "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."--Jacket