Natural Compounds as Drugs, Volume I (eBook)

Contents 6
Foreword 8
Glossary 12
Mother Nature’s gifts to diseases of man: the impact of natural products on anti-infective, anticholestemics and anticancer drug discovery 14
Abstract 15
1 Introduction to natural products 15
2 Anti-infectives (antibacterials, antifungals and antiparasitics) 17
3 Anticholestemics 32
4 Anticancer 33
5 Conclusion 42
References 44
Drug discovery and development with plant- derived compounds 57
Abstract 58
1 Introduction 58
2 The discovery process of biologically active plant products 62
3 Anticancer agents 64
4 Antimalarial agents 81
5 Antiviral agents 86
6 Inflammation, nociception, immune system 93
7 Cardiovascular and metabolic disorders 102
8 Alzheimer’s disease 108
9 Industrial scale production of plant derived drugs – supply and conservation issues 113
10 Plant-derived drug discovery after the convention on biological diversity 116
11 Conclusions 118
References 118
Evolutionary mechanisms underlying secondary metabolite diversity 130
Abstract 131
1 Introduction 131
2 Evolution of secondary metabolite biosynthesis enzymes from primary metabolism 132
3 Factors influencing the distribution of biosynthetic enzymes among species 135
4 Mechanisms leading to the diversification of enzymes and their products 139
5 Hypotheses about functional roles of secondary metabolites 143
6 Role of selection and adaptation on the evolution of secondary metabolites 145
References 147
Biodiversity, chemical diversity and drug discovery 151
Abstract 152
1 Introduction 152
2 Microbial sources 153
3 Microbial diversity 158
4 Role of terrestrial and marine habitats 161
5 Microbial diversity and dereplication of strains 163
6 Exploiting the hidden microbial diversity 164
7 High throughput isolation approaches 168
8 Genomics-guided natural products discovery 169
9 Chemical diversity 171
10 Drug discovery 176
References 177
High impact technologies for natural products screening 184
Abstract 185
1 Introduction 185
2 Construction and characterization of natural products libraries 188
3 Screening of natural products libraries 204
4 Conclusion 211
References 212
Virtual screening for the discovery of bioactive natural products 219
Abstract 220
1 Introduction 220
2 Status of NPs 221
3 Holistic versus molecular approaches in drug discovery from nature 222
4 Computational approaches for the discovery of lead structures from nature 224
5 Pharmacophore concept in NP research 227
6 Structure-based pharmacophore model 228
7 Ligand-based pharmacophore model 232
8 Discriminant analysis 235
9 Databases 236
10 Integrated strategies for the discovery of bioactive NPs 238
11 Conclusion 247
References 251
Strain improvement for production of pharmaceuticals and other microbial metabolites by fermentation 257
Abstract 258
1 Introduction 258
2 Mutagenesis 259
3 Deciphering biosynthetic pathways 266
4 Recombination 266
5 Genetic engineering 271
6 New strategies 273
Closing comments 279
References 280
Nutritional and engineering aspects of microbial process development 295
Abstract 296
1 Introduction 296
2 Engineering aspects 314
3 Summary 326
References 326
Natural products from plant cell cultures 332
Abstract 333
1 Introduction 333
2 Techniques of plant cell culture 336
3 Natural products produced from plant cell culture 342
4 Future directions 363
References 364