Specialists in drug design and discovery of zinc metalloprotein inhibitors report on research findings that have emerged over the past few years at a level accessible to academic or industrial researchers and to graduate students. They cover carbonic anhydrase inhibitors and activators, matrix metalloproteinase inhibitors, bacterial zinc protease inhibitors, and other enzymes containing zinc. Among specific topics are anti-glaucoma carbonic anhydrase inhibitors as opthalmologic drugs, crystallographic studies of carbonic anydrases from fungal pathogens for structure-assisted drug development, sulfonylated matrix metalloproteinase inhibitors, Clostridium histolyticum collagenase inhibitors in the drug design, angiotensin converting enzyme inhibitors, and inhibitors of histidinol dehydrogenases as antibacterial agents. Annotation ©2010 Book News, Inc., Portland, OR (booknews.com)
Brings together functional and structural informationrelevant to the design of drugs targeting zinc enzymesThe 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.
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 DAmbrosio, 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. Muhlschlegel).
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, Francøois Turtaut, Stephan Kohler, 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.
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.
