Plant Bioactives and Drug Discovery

<p>Contributors xv</p>
<p>Preface xix</p>
<p>1 Natural Products in Drug Discovery: Recent Advances 1<br /> Gordon M. Cragg, Paul G. Grothaus, and David J. Newman</p>
<p>1.1 Introduction 1</p>
<p>1.2 The Role of Traditional Medicine and Plants in Drug Discovery 2</p>
<p>1.3 The Role of Marine Organisms in Drug Discovery 4</p>
<p>1.4 The Role of Microorganisms in Drug Discovery: An Historical Perspective 6</p>
<p>1.5 Other Sources 8</p>
<p>1.6 The Importance of Natural Products in Drug Discovery and Development 8</p>
<p>1.7 Classical Natural Sources: Untapped Potential 10</p>
<p>1.8 The Unexplored Potential of Microbial Diversity 10</p> 1.9 Development of Drugs From Natural Products: A Multidisciplinary Process 19
<p>1.10 Conclusions 26</p>
<p>References 27</p>
<p>2 Modern Approaches in the Search for New Active Compounds from Crude Extracts of Natural Sources 43<br /> Emerson F. Queiroz, Kurt Hostettmann, and Jean–Luc Wolfender</p>
<p>2.1 Introduction 43</p>
<p>2.2 Selection of the Natural Matrices 45</p>
<p>2.3 Rapid Online Identification and Dereplication 46</p>
<p>2.4 HPLC–Hyphenated Methods for Natural Product Identification 46</p> 2.5 Studies on Natural Products Using LC–NMR, Microflow NMR, and SPE–NMR 57
<p>2.6 Application of Direct NMR Methods for Chemical Profiling of Crude Extracts 67</p> 2.7 Conclusions 69
<p>References 71</p>
<p>3 Natural Products as Lead Compounds in Medicinal Chemistry 81<br /> Eliezer J. Barreiro, Carlos A. M. Fraga, and Lidia M. Lima</p>
<p>3.1 Medicinal Chemistry Definition and the Importance of the Lead Compound in Drug Discovery 81</p>
<p>3.2 Natural Products as Drugs 84</p> 3.4 Natural Products as Lead Compounds for New Drug Candidates 107
<p>3.5 Conclusions 113</p>
<p>Acknowledgments 115</p>
<p>References 115</p>
<p>4 The Importance of Structural Manipulation of Natural Compounds in Drug Discovery and Development 127<br /> Arturo San Feliciano, Mar&iacute;a &Aacute; . Castro, Jos&eacute; L. L&oacute;pez–Perez, and Esther del Olmo</p>
<p>4.1 Introduction 127</p>
<p>4.2 Chemomodulation of Podophyllotoxin Cyclolignans 132</p> 4.3 Chemoinduction of Bioactivity on Dihydrostilbenoids 140
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<br /> 4.4 Chemoinduction and Chemomodulation of the Antiparasitic Activity of Stilbenoids 150
<p>4.5 Conclusions 152</p>
<p>Acknowledgments 153</p>
<p>References 153</p>
<p>5 The Action of Plants and their Constituents on the Central Nervous System 161<br /> F&uacute;lvio R. Mendes, Giuseppina Negri, Joaquim M. Duarte–Almeida, Ricardo Tabach, and Elisaldo A. Carlini</p>
<p>5.1 Introduction 161</p>
<p>5.2 Plants with CNS Depressant Activity 162</p> 5.3 Plants with the CNS Stimulant Activity 169
<p>5.4 Plants Used as Antidepressants 174</p> 5.5 Adaptogenic Plants 175
<p>5.6 Plants Used to Treat Neurodegenerative Diseases 178</p> 5.7 Plants with the Mind–Altering Activity 182
<p>5.8 Plants Used Against Drug Dependence 188</p>
<p>5.9 Conclusions 188</p>
<p>Acknowledgments 191</p>
<p>References 191</p>
<p>6 The Role of Natural Products in Discovery of New Anti–Infective Agents with Emphasis on Antifungal Compounds 205<br /> Maximiliano Sortino, Marcos Derita, Laura Svetaz, Marcela Raimondi, Melina Di Liberto, Elisa Petenatti, Mahabir Gupta, and Susana Zacchino</p>
<p>6.1 Infectious Diseases and Available Antimicrobial Agents 205</p>
<p>6.2 Fungal Infections and Available Antifungal Agents 206</p> 6.3 The Need of New Antifungal Agents 208
<p>6.4 From Antifungal Compounds to Antifungal Drugs: Some Considerations 223</p>
<p>6.5 Other Strategies Based on Non–targeted Assays 223</p>
<p>6.6 Strategies Based on Targeted Assays for the Discovery of Antifungal Compounds 226</p> 6.7 Conclusion 229
<p>References 229</p>
<p>7 Antiulcer Agents from Higher Plants 241<br /> Luiz C. Klein–J&uacute;nior, Jos&eacute; R. Santin, and S&eacute;rgio F. de Andrade</p>
<p>7.1 Introduction 241</p>
<p>7.2 Medicinal Plants with Antiulcer Activity 243</p> 7.3 Secondary Metabolites as a Source of Anti–Ulcer Drug Leads 251
<p>7.4 Conclusions 256</p>
<p>References 256</p>
<p>8 Recent Progress in the Chemistry and Biology of Paclitaxel (TaxolTM) and Related Taxanes 263<br /> Jun Qi, Jielu Zhao, and David G. I. Kingston</p>
<p>8.1 Introduction 263</p>
<p>8.2 New Chemistry of Paclitaxel 265</p> 8.3 Tubulin Binding 295
<p>8.4 Pharmacology of Paclitaxel 306</p>
<p>8.5 Conclusions 318</p>
<p>References 319</p>
<p>9 Cancer Chemopreventive Activity of Higher Plants 337<br /> A. Douglas Kinghorn, Yulin Ren, Jie Li, and Chung Ki Sung</p>
<p>9.1 Introduction 337</p>
<p>9.2 Potental Cancer Chemopreventive Agents from Selected Dietary Higher Plants 338</p>
<p>9.3 Conclusions 348</p>
<p>Acknowledgments 348</p>
<p>References 348</p>
<p>10 Medicinal Plants and Pharmaceutical Technology 359<br /> Ruth M. Lucinda da Silva, Ang&eacute;lica G. Couto, and Tania M.B. Bresolin</p>
<p>10.1 Introduction 359</p>
<p>10.2 Supply of Herbal Materials 361</p>
<p>10.3 Harvest and Postharvest Processing 363</p> 10.4 Extraction of Herbal Drugs 365
<p>10.5 Dry Extracts 369</p>
<p>10.6 Phytopharmaceutical Dosage Forms 373</p> 10.7 Quality Assurance and Quality Control of Herbal Drugs and Phytopharmaceuticals 377
<p>References 387</p>
<p>11 Natural Products in Clinical Trials 395<br /> Sigrun Chrubasik</p>
<p>11.1 The Quality of Clinical Trials 395</p>
<p>11.2 Examples of Clinical Studies with Natural Products 396</p>
<p>11.3 Evidence of Effectiveness 413</p>
<p>References 416</p>
<p>12 The Influence of Biotic and Abiotic Factors on the Production of Secondary Metabolites in Medicinal Plants 419<br /> Dayana R. Gouvea, Leonardo Gobbo–Neto, and Norberto P. Lopes</p>
<p>12.1 Introduction 419</p>
<p>12.2 Biotic and Abiotic Factors that can Affect Biosynthesis and/or Metabolites Accumulation 422</p> 12.3 Types of Observed Variations on Secondary Metabolites Content 431
<p>12.4 Conclusions 439</p>
<p>References 440</p>
<p>13 Production of Bioactives Compounds: The Importance of Pictet Spengler Reaction in the XXI Century 453<br /> Pilar Menendez, Ilaria D Acquarica, Giuliano Delle Monache, Francesca Ghirga, Andrea Calcaterra, Marco Barba, Alberto Macone, Alberto Boffi, Alessandra Bonamore, and Bruno Botta</p>
<p>13.1 Introduction 453</p>
<p>13.2 Variants and Applications 455</p>
<p>13.3 Asymmetric Synthesis 457</p>
<p>13.4 Chiral Auxiliary and Enantioselective Catalysis 459</p>
<p>13.5 Enzymatic Catalysis 465</p>
<p>13.6 The Pictet Spengler Reaction at Present 468</p> 13.7 Conclusions 478
<p>Acknowledgment 480</p>
<p>References 480</p>
<p>14 Screening Methods for Drug Discovery from Plants 489<br /> Alan L. Harvey</p>
<p>14.1 From Traditional to Phenotypic Screening 489</p>
<p>14.2 Molecular and Cellular Assays 490</p>
<p>14.3 Disease–Specific Assays 492</p> 14.4 Conclusions 495
<p>References 495</p>
<p>15 Phytotherapeutics Intellectual Property Rights, Global Market, and Global Regulatory Guidelines 499<br /> James D. McChesney, Raymond Cooper, and Kip Vought</p>
<p>15.1 Intellectual Property Rights 499</p>
<p>15.2 Biodiversity 501</p>
<p>15.3 Global Market Perspectives 502</p> 15.4 Regulatory Perspectives 507
<p>15.5 Conclusions 525</p>
<p>References 526</p>
<p>16 Cooperation Between the Pharmaceutical Industry and Academic Institutions in Drug Discovery 529<br /> Valdir Cechinel–Filho, Rivaldo Niero, and Rosendo A. Yunes</p>
<p>16.1 Introduction 529</p>
<p>16.2 Interaction Between Academic Institutions and the Pharmaceutical Industry 530</p>
<p>16.3 Overview of the Global Pharmaceutical Market 534</p>
<p>16.4 Reorganization of the Pharmaceutical Industry 535</p> 16.5 Conclusions 541
<p>Acknowledgments 542</p>
<p>References 542</p>
<p>Index 545</p>