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.

• Preface ixContributors xiPart I Introduction 11. Introduction to Zinc Enzymes as Drug Targets 3Claudiu T. Supuran and Jean-Yves WinumPart II Drug Design of Carbonic Anhydrase Inhibitors and Activators 132. Carbonic Anhydrases as Drug Targets: General Presentation 15Claudiu T. Supuran3. Zinc Binding Functions in the Design of Carbonic Anhydrase Inhibitors 39Jean-Yves Winum, Jean-Louis Montero, Andrea Scozzafava, and Claudiu T. Supuran4. X-Ray Crystallography of Carbonic Anhydrase Inhibitors and Its Importance in Drug Design 73Vincenzo Alterio, Anna Di Fiore, Katia D’Ambrosio, Claudiu T. Supuran, and Giuseppina De Simone5. Antiglaucoma Carbonic Anhydrase Inhibitors as Ophthalomologic Drugs 139Francesco Mincione, Andrea Scozzafava, and Claudiu T. Supuran6. Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs 155Daniela Vullo, Alessio Innocenti, and Claudiu T. Supuran7. Drug Design of Carbonic Anhydrase Inhibitors as Anticonvulsant Agents 171Anne Thiry, Jean-Michel Dogne, Claudiu T. Supuran, and Bernard Masereel8. Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII 193Silvia Pastorekova, Monika Barathova, Juraj Kopacek, and Jaromir Pastorek9. Fluorescent- and Spin-Labeled Sulfonamides as Probe for Carbonic Anhydrase IX 223Alessandro Cecchi, Laura Ciani, Sandra Ristori, and Claudiu T. Supuran10. Drug Design of Antiobesity Carbonic Anhydrase Inhibitors 241Giuseppina De Simone and Claudiu T. Supuran11. Dual Carbonic Anhydrase and Cyclooxygenase-2 Inhibition 255Jean-Michel Dogne, Anne Thiry, Bernard Masereel, and Claudiu T. Supuran12. Advances in the Inhibitory and Structural Investigations on Carbonic Anhydrase Isozymes XIII and XV 273Mika Hilvo, Giuseppina De Simone, Claudiu T. Supuran, and Seppo Parkkila13. Mechanism and Inhibition of the b-Class and c-Class Carbonic Anhydrases 285James G. Ferry and Claudiu T. Supuran14. Fungal and Nematode Carbonic Anhydrases: Their Inhibition in Drug Design 301Rebecca A. Hall and Fritz. A. M€uhlschlegel15. Crystallographic Studies on Carbonic Anhydrases from Fungal Pathogens for Structure-Assisted Drug Development 323Uta-Maria Ohndorf, Christine Schlicker, and Clemens Steegborn16. Malaria Parasite Carbonic Anhydrase and Its Inhibition in the Development of Novel Therapies of Malaria 335Jerapan Krungkrai, Sudaratana R. Krungkrai, and Claudiu T. Supuran17. Inhibitors of Helicobacter pylori a- and b-Carbonic Anhydrases as Novel Drugs for Gastroduodenal Diseases 359Isao Nishimori, Hiroaki Takeuchi, and Claudiu T. Supuran18. QSAR of Carbonic Anhydrase Inhibitors and Their Impact on Drug Design 375Adriano Martinelli and Tiziano Tuccinardi19. Selectivity Issues in the Design of CA Inhibitors 399Claudiu T. Supuran and Jean-Yves Winum20. Bicarbonate Transport Metabolons 415Danielle E. Johnson and Joseph R. Casey21. Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors 439Marc A. Ilies22. Drug Design Studies of Carbonic Anhydrase Activators 473Claudia Temperini, Andrea Scozzafava, and Claudiu T. SupuranPart III Drug Design of Matrix Metalloproteinase Inhibitors 48723. Matrix Metalloproteinases: An Overview 489Hideaki Nagase and Robert Visse24. MMP Inhibitors Based on Earlier Succinimide Strategies: From Early to New Approaches 519M. Amélia Santos25. Drug Design of Sulfonylated MMP Inhibitors 549Armando Rossello and Elisa Nuti26. ADAMs and ADAMTs Selective Synthetic Inhibitors 591Armando Rossello, Elisa Nuti, and Alfonso Maresca27. QSAR Studies of MMP Inhibitors 647Tiziano Tuccinardi and Adriano MartinelliPart IV Drug Design of Bacterial Zinc Protease Inhibitors 67328. Bacterial Zinc Proteases as Orphan Targets 675Claudiu T. Supuran29. Botulinus Toxin, Tetanus Toxin, and Anthrax Lethal Factor Inhibitors 705Antonio Mastrolorenzo and Claudiu T. Supuran30. Clostridium histolyticum Collagenase Inhibitors in the Drug Design 721Claudiu T. Supuran31. Other Bacterial Zinc Peptidases as Potential Drug Targets 731Kunihiko WatanabePart V Drug Design Studies of other Zinc-containing Enzymes 74932. Angiotensin Converting Enzyme (ACE) Inhibitors 751Ana Camara-Artigas, Vicente Jara-Perez, and Montserrat Andujar-Sanchez33. P-III Metalloproteinase (Leucurolysin-B) from Bothrops leucurus Venom: Isolation and Possible Inhibition 789Eladio F. Sanchez and Johannes A. Eble34. CaaX-Protein Prenyltransferase Inhibitors 813Martin Schlitzer, Regina Ortmann, and Mirko Altenk€amper35. Histone Deacetylase Inhibitors 859Paul W. Finn36. Recent Development of Diagnostic and Therapeutic Agents Targeting Glutamate Carboxypeptidase II (GCPII) 881Youngjoo Byun, Ronnie C. Mease, Shawn E. Lupold, and Martin G. Pomper37. Targeting HIV-1 Integrase Zinc Binding Motif 911Mario Sechi, Mauro Carcelli, Dominga Rogolino, and Nouri Neamati38. Inhibitors of Histidinol Dehydrogenases as Antibacterial Agents 937Pascale Joseph, François Turtaut, Stephan K€ohler, and Jean-Yves Winum39. Dihydroorotase Inhibitors 951Mihwa Lee, Megan J. Maher, Richard I. Christopherson, and J. Mitchell Guss40. APOBEC3G: A Promising Antiviral Target 981Claudiu T. Supuran and Jean-Yves WinumIndex 989

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.

• Preface ixContributors xiPart I Introduction 11. Introduction to Zinc Enzymes as Drug Targets 3Claudiu T. Supuran and Jean-Yves WinumPart II Drug Design of Carbonic Anhydrase Inhibitors and Activators 132. Carbonic Anhydrases as Drug Targets: General Presentation 15Claudiu T. Supuran3. Zinc Binding Functions in the Design of Carbonic Anhydrase Inhibitors 39Jean-Yves Winum, Jean-Louis Montero, Andrea Scozzafava, and Claudiu T. Supuran4. X-Ray Crystallography of Carbonic Anhydrase Inhibitors and Its Importance in Drug Design 73Vincenzo Alterio, Anna Di Fiore, Katia D’Ambrosio, Claudiu T. Supuran, and Giuseppina De Simone5. Antiglaucoma Carbonic Anhydrase Inhibitors as Ophthalomologic Drugs 139Francesco Mincione, Andrea Scozzafava, and Claudiu T. Supuran6. Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs 155Daniela Vullo, Alessio Innocenti, and Claudiu T. Supuran7. Drug Design of Carbonic Anhydrase Inhibitors as Anticonvulsant Agents 171Anne Thiry, Jean-Michel Dogne, Claudiu T. Supuran, and Bernard Masereel8. Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII 193Silvia Pastorekova, Monika Barathova, Juraj Kopacek, and Jaromir Pastorek9. Fluorescent- and Spin-Labeled Sulfonamides as Probe for Carbonic Anhydrase IX 223Alessandro Cecchi, Laura Ciani, Sandra Ristori, and Claudiu T. Supuran10. Drug Design of Antiobesity Carbonic Anhydrase Inhibitors 241Giuseppina De Simone and Claudiu T. Supuran11. Dual Carbonic Anhydrase and Cyclooxygenase-2 Inhibition 255Jean-Michel Dogne, Anne Thiry, Bernard Masereel, and Claudiu T. Supuran12. Advances in the Inhibitory and Structural Investigations on Carbonic Anhydrase Isozymes XIII and XV 273Mika Hilvo, Giuseppina De Simone, Claudiu T. Supuran, and Seppo Parkkila13. Mechanism and Inhibition of the b-Class and c-Class Carbonic Anhydrases 285James G. Ferry and Claudiu T. Supuran14. Fungal and Nematode Carbonic Anhydrases: Their Inhibition in Drug Design 301Rebecca A. Hall and Fritz. A. M€uhlschlegel15. Crystallographic Studies on Carbonic Anhydrases from Fungal Pathogens for Structure-Assisted Drug Development 323Uta-Maria Ohndorf, Christine Schlicker, and Clemens Steegborn16. Malaria Parasite Carbonic Anhydrase and Its Inhibition in the Development of Novel Therapies of Malaria 335Jerapan Krungkrai, Sudaratana R. Krungkrai, and Claudiu T. Supuran17. Inhibitors of Helicobacter pylori a- and b-Carbonic Anhydrases as Novel Drugs for Gastroduodenal Diseases 359Isao Nishimori, Hiroaki Takeuchi, and Claudiu T. Supuran18. QSAR of Carbonic Anhydrase Inhibitors and Their Impact on Drug Design 375Adriano Martinelli and Tiziano Tuccinardi19. Selectivity Issues in the Design of CA Inhibitors 399Claudiu T. Supuran and Jean-Yves Winum20. Bicarbonate Transport Metabolons 415Danielle E. Johnson and Joseph R. Casey21. Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors 439Marc A. Ilies22. Drug Design Studies of Carbonic Anhydrase Activators 473Claudia Temperini, Andrea Scozzafava, and Claudiu T. SupuranPart III Drug Design of Matrix Metalloproteinase Inhibitors 48723. Matrix Metalloproteinases: An Overview 489Hideaki Nagase and Robert Visse24. MMP Inhibitors Based on Earlier Succinimide Strategies: From Early to New Approaches 519M. Amélia Santos25. Drug Design of Sulfonylated MMP Inhibitors 549Armando Rossello and Elisa Nuti26. ADAMs and ADAMTs Selective Synthetic Inhibitors 591Armando Rossello, Elisa Nuti, and Alfonso Maresca27. QSAR Studies of MMP Inhibitors 647Tiziano Tuccinardi and Adriano MartinelliPart IV Drug Design of Bacterial Zinc Protease Inhibitors 67328. Bacterial Zinc Proteases as Orphan Targets 675Claudiu T. Supuran29. Botulinus Toxin, Tetanus Toxin, and Anthrax Lethal Factor Inhibitors 705Antonio Mastrolorenzo and Claudiu T. Supuran30. Clostridium histolyticum Collagenase Inhibitors in the Drug Design 721Claudiu T. Supuran31. Other Bacterial Zinc Peptidases as Potential Drug Targets 731Kunihiko WatanabePart V Drug Design Studies of other Zinc-containing Enzymes 74932. Angiotensin Converting Enzyme (ACE) Inhibitors 751Ana Camara-Artigas, Vicente Jara-Perez, and Montserrat Andujar-Sanchez33. P-III Metalloproteinase (Leucurolysin-B) from Bothrops leucurus Venom: Isolation and Possible Inhibition 789Eladio F. Sanchez and Johannes A. Eble34. CaaX-Protein Prenyltransferase Inhibitors 813Martin Schlitzer, Regina Ortmann, and Mirko Altenk€amper35. Histone Deacetylase Inhibitors 859Paul W. Finn36. Recent Development of Diagnostic and Therapeutic Agents Targeting Glutamate Carboxypeptidase II (GCPII) 881Youngjoo Byun, Ronnie C. Mease, Shawn E. Lupold, and Martin G. Pomper37. Targeting HIV-1 Integrase Zinc Binding Motif 911Mario Sechi, Mauro Carcelli, Dominga Rogolino, and Nouri Neamati38. Inhibitors of Histidinol Dehydrogenases as Antibacterial Agents 937Pascale Joseph, François Turtaut, Stephan K€ohler, and Jean-Yves Winum39. Dihydroorotase Inhibitors 951Mihwa Lee, Megan J. Maher, Richard I. Christopherson, and J. Mitchell Guss40. APOBEC3G: A Promising Antiviral Target 981Claudiu T. Supuran and Jean-Yves WinumIndex 989

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.

• Preface ixContributors xiPart I Introduction 11. Introduction to Zinc Enzymes as Drug Targets 3Claudiu T. Supuran and Jean-Yves WinumPart II Drug Design of Carbonic Anhydrase Inhibitors and Activators 132. Carbonic Anhydrases as Drug Targets: General Presentation 15Claudiu T. Supuran3. Zinc Binding Functions in the Design of Carbonic Anhydrase Inhibitors 39Jean-Yves Winum, Jean-Louis Montero, Andrea Scozzafava, and Claudiu T. Supuran4. X-Ray Crystallography of Carbonic Anhydrase Inhibitors and Its Importance in Drug Design 73Vincenzo Alterio, Anna Di Fiore, Katia D’Ambrosio, Claudiu T. Supuran, and Giuseppina De Simone5. Antiglaucoma Carbonic Anhydrase Inhibitors as Ophthalomologic Drugs 139Francesco Mincione, Andrea Scozzafava, and Claudiu T. Supuran6. Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs 155Daniela Vullo, Alessio Innocenti, and Claudiu T. Supuran7. Drug Design of Carbonic Anhydrase Inhibitors as Anticonvulsant Agents 171Anne Thiry, Jean-Michel Dogne, Claudiu T. Supuran, and Bernard Masereel8. Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII 193Silvia Pastorekova, Monika Barathova, Juraj Kopacek, and Jaromir Pastorek9. Fluorescent- and Spin-Labeled Sulfonamides as Probe for Carbonic Anhydrase IX 223Alessandro Cecchi, Laura Ciani, Sandra Ristori, and Claudiu T. Supuran10. Drug Design of Antiobesity Carbonic Anhydrase Inhibitors 241Giuseppina De Simone and Claudiu T. Supuran11. Dual Carbonic Anhydrase and Cyclooxygenase-2 Inhibition 255Jean-Michel Dogne, Anne Thiry, Bernard Masereel, and Claudiu T. Supuran12. Advances in the Inhibitory and Structural Investigations on Carbonic Anhydrase Isozymes XIII and XV 273Mika Hilvo, Giuseppina De Simone, Claudiu T. Supuran, and Seppo Parkkila13. Mechanism and Inhibition of the b-Class and c-Class Carbonic Anhydrases 285James G. Ferry and Claudiu T. Supuran14. Fungal and Nematode Carbonic Anhydrases: Their Inhibition in Drug Design 301Rebecca A. Hall and Fritz. A. M€uhlschlegel15. Crystallographic Studies on Carbonic Anhydrases from Fungal Pathogens for Structure-Assisted Drug Development 323Uta-Maria Ohndorf, Christine Schlicker, and Clemens Steegborn16. Malaria Parasite Carbonic Anhydrase and Its Inhibition in the Development of Novel Therapies of Malaria 335Jerapan Krungkrai, Sudaratana R. Krungkrai, and Claudiu T. Supuran17. Inhibitors of Helicobacter pylori a- and b-Carbonic Anhydrases as Novel Drugs for Gastroduodenal Diseases 359Isao Nishimori, Hiroaki Takeuchi, and Claudiu T. Supuran18. QSAR of Carbonic Anhydrase Inhibitors and Their Impact on Drug Design 375Adriano Martinelli and Tiziano Tuccinardi19. Selectivity Issues in the Design of CA Inhibitors 399Claudiu T. Supuran and Jean-Yves Winum20. Bicarbonate Transport Metabolons 415Danielle E. Johnson and Joseph R. Casey21. Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors 439Marc A. Ilies22. Drug Design Studies of Carbonic Anhydrase Activators 473Claudia Temperini, Andrea Scozzafava, and Claudiu T. SupuranPart III Drug Design of Matrix Metalloproteinase Inhibitors 48723. Matrix Metalloproteinases: An Overview 489Hideaki Nagase and Robert Visse24. MMP Inhibitors Based on Earlier Succinimide Strategies: From Early to New Approaches 519M. Amélia Santos25. Drug Design of Sulfonylated MMP Inhibitors 549Armando Rossello and Elisa Nuti26. ADAMs and ADAMTs Selective Synthetic Inhibitors 591Armando Rossello, Elisa Nuti, and Alfonso Maresca27. QSAR Studies of MMP Inhibitors 647Tiziano Tuccinardi and Adriano MartinelliPart IV Drug Design of Bacterial Zinc Protease Inhibitors 67328. Bacterial Zinc Proteases as Orphan Targets 675Claudiu T. Supuran29. Botulinus Toxin, Tetanus Toxin, and Anthrax Lethal Factor Inhibitors 705Antonio Mastrolorenzo and Claudiu T. Supuran30. Clostridium histolyticum Collagenase Inhibitors in the Drug Design 721Claudiu T. Supuran31. Other Bacterial Zinc Peptidases as Potential Drug Targets 731Kunihiko WatanabePart V Drug Design Studies of other Zinc-containing Enzymes 74932. Angiotensin Converting Enzyme (ACE) Inhibitors 751Ana Camara-Artigas, Vicente Jara-Perez, and Montserrat Andujar-Sanchez33. P-III Metalloproteinase (Leucurolysin-B) from Bothrops leucurus Venom: Isolation and Possible Inhibition 789Eladio F. Sanchez and Johannes A. Eble34. CaaX-Protein Prenyltransferase Inhibitors 813Martin Schlitzer, Regina Ortmann, and Mirko Altenk€amper35. Histone Deacetylase Inhibitors 859Paul W. Finn36. Recent Development of Diagnostic and Therapeutic Agents Targeting Glutamate Carboxypeptidase II (GCPII) 881Youngjoo Byun, Ronnie C. Mease, Shawn E. Lupold, and Martin G. Pomper37. Targeting HIV-1 Integrase Zinc Binding Motif 911Mario Sechi, Mauro Carcelli, Dominga Rogolino, and Nouri Neamati38. Inhibitors of Histidinol Dehydrogenases as Antibacterial Agents 937Pascale Joseph, François Turtaut, Stephan K€ohler, and Jean-Yves Winum39. Dihydroorotase Inhibitors 951Mihwa Lee, Megan J. Maher, Richard I. Christopherson, and J. Mitchell Guss40. APOBEC3G: A Promising Antiviral Target 981Claudiu T. Supuran and Jean-Yves WinumIndex 989