Drug Discovery from Nature

Передня обкладинка
S. Grabley, R. Thiericke
Springer Science & Business Media, 26 лист. 1998 р. - 347 стор.
Drug discovery strategies for both pharmaceutical and agrochemical applications are at a stage of rapid development. More than 30 % of sales of drugs for human consumption worldwide are of plant origin. This unique book covers the present status and future potential of natural products in drug discovery. It provides the reader with recent information regarding the impact on drug discovery, development and strategies, technical and automation aspects, and methods based on biochemistry as well as molecular biology, highlighting compounds from natural sources. Special emphasis is placed on the various strategies to gain access to natural compounds and combinatorial approaches by making use of both synthetic and biological methods. Because the renewed interest in the use of natural sources in drug discovery is an important supplement to combinatorial and parallel synthesis approaches, this book is timely and will have a great scientific impact.
 

Зміст

The Impact of Natural Products on Drug Discovery
3
12 Historical Issues of Drugs from Nature
5
122 Acetysalicylic Acid
7
123 Antibiotics
9
124 Further Developments
10
13 New Drugs from Microorganisms
11
133 Antihypercholesterolemic Drugs
13
134 Antidiabetic Drugs
16
968 Ripostatin
163
969 Sorangiolid
164
9611 Crocacin
165
9612 Gephyronic Acid
166
9614 Cittilin
167
9615 Myxochromid
168
97 Derivatives and Total Syntheses of Myxobacterial Compounds
169
99 Not all Myxobacterial Species are Equally Good Producers
171

Hormone Antagonists
17
136 Anticancer Drugs
18
14 New Drugs from Plants
20
142 Anticancer Drugs
22
143 Drugs for Various Applications
25
15 The Marine Environment
26
16 Perspectives
31
References
33
Recent Developments in Drug Discovery Technologies
38
22 Potential Impact of Genomic Sciences
39
222 Analytical Methods
40
223 Applicational Aspects of Gene Function Analysis
41
23 HighThroughput Screening Assays
43
24 Sample Supply in HighThroughput Screening
46
References
47
Technical Aspects
49
A Central Natural Product Pool New Approach in Drug Discovery Strategies
51
32 Concept
52
Proprietary Rights and Other Guidelines
53
34 Incentives
54
References
55
Automation Strategies in Drug Discovery
56
42 History
57
43 Economic Aspects
58
44 Sample Sourcing
60
442 Natural Sources
62
46 Screening Systems
64
47 DataHandling
68
48 Conclusion
69
Synergistic Use of Combinatorial and Natural Product Chemistry
72
52 Combinatorial Chemistry Short Summary
73
521 Solid Phase Synthesis
74
5212 Linkers
75
523 Design of Libraries
76
524 Product Quality
77
53 Biopolymers
78
533 Oligosaccharides
80
534 Polyketides
81
54 Natural Product Derivatives
82
541 NonAlkaloid Natural Product Derivatives
84
5412 Balanol
85
542 Alkaloids
87
5422 Spiroindolines
88
5425 Quinolines
89
5425 Isoqulnalines
90
5427 Quinazolinediones
91
553 Other Natural Products as Templates
93
56 Future Potential
101
Supercritical Fluid Extraction SFE Novel Strategies in the Processing of Biomaterials
106
62 Properties of Supercritical Fluids SF
107
63 Supercritical Carbon Dioxide SCCO
108
64 Extraction of Polar and Ionic Compounds
109
66 Potential and Applications of SFE for the Pharmaceutical Industry
110
662 Extraction of Antibiotics
111
67 Concluding Remarks
112
Natural Products from Microbial Sources
115
From Past to Present
117
73 The 1960s and 1970s
118
74 Secondary Metabolites as Pharmacological Agents and New Screening Approaches
119
75 Biosynthetic Modifications of Structures and Outlook
120
References
121
CHAPTER 8 The Chemical Screening Approach
124
83 PhysicoChemical Screening
128
84 Chemical Screening
130
842 New Metabolites
132
85 Further Development
139
86 Discussion
141
862 Future Potential
144
Myxobacteria as Producers of Secondary Metabolites
149
92 Myxobacteria are Common but Unusual Soil Bacteria
150
93 Many Interesting Substances have been Found in Myxobacteria
154
94 Myxobacterial Compounds Belong to Quite Different Chemical Classes
155
96 Examples of More Recently Discovered Myxobacterial Compounds
156
962 Epothilon
157
963 Chondramid
159
965 Ratjadon
160
966 Disorazol
161
967 Chivosazol
162
910 The Genetics of Myxobacterial Secondary Metabolism
174
9103 Myxovirescin
175
911 A Historical Note
176
References
177
Trends in Marine Biotechnology
180
103 Isolation and Culturing of Marine Microorganisms
181
104 Natural Product Chemistry and Biological Activity of Marine Microorganism Derived Secondary Metabolites
182
105 The Future
185
Biochemistry and Molecular Biology Based Methods
189
Structure Modification via Biological Derivatization Methods
191
112 Biological Derivatization Methods and History
192
114 PrecursorDirected Biosynthesis
194
115 NonEnymatic Biotransformation
198
117 Enzyme inhibition
199
118 Mutasynthesis
200
119 Hybrid Natural Products by Genetic Engineering
201
1110 Enzymatic Catalysis
202
11102 Reconstitution of Biosynthetic Pathways In Vitro
203
11103 Enzymatic Catalysis in Carbohydrate Synthesis
204
1111 Conclusion
206
References
209
Molecular Biological Aspects of Antibiotic Biosynthesis
215
122 Strategies for Cloning Antibiotic Biosynthesis Genes
217
1222 Hybridization with Heterologous Probes
218
1223 Cloning Biosynthetic Genes via Resistance Genes
219
1224 Reverse Genetics
220
1225 Cloning Based on Consensus Sequences
221
1232 Altering the Regulation of Gene Transcription
222
1233 Improving Product Spectrum
223
1234 Reengineering Biosynthesis to Produce New Compounds
225
124 Future Prospects and Limitations
227
1241 Combinatorial Biosynthesis
229
1243 Expression of Genes from Uncultivable Organisms
230
Combinatorial Biosynthesis of Antibiotics
233
1322 Basic Requirements for the Production of Hybrid Antibiotics
236
133 Hybrid Antibiotics Produced by Combinatorial Biosynthesis
237
1332 By Manipulation of Iterative Type II Polyketide Synthase Genes
244
1333 By Manipulation of Genes for the Polyketide Tailoring Enzymes
248
1334 By Manipulation of Oligopeptide Synthetase Genes
251
References
252
Aspects in Application
255
Impact of Natural Products on Cell Biology LowMolecular Mass Effectors of Folding Helper Proteins
257
142 PeptidylProlyl cistrans Isomerases
259
1422 Prolyl Isomerizations as Slow Steps in Protein Folding
260
1423 Classification and Properties of Peptidyl Prolyl cistrans Isomerases
261
143 Natural Inhibitors of Peptidyl Prolyl cistrans Isomerases
263
1432 FK506
268
1433 Rapamycin
269
1434 Meridamycin Antascomicins Hymenistatin
272
144 The Gain of Function Model of Immunosuppression
275
145 Summary
277
Novel Antibacterial Drugs from Microorganisms
281
152 Directed Screens for New Antibiotics and SiteDirected New Antibacterials
282
153 New NarrowSpectrum Antibiotics
284
154 New Structural Variations of Antibacterial Lead Structures
287
1542 Macrolides
289
1543 Tetracyclines
290
1545 Ansamycins
291
155 Bacteriocins and Antibiotics
292
1551 Polyethers
293
157 Summary and Outlook
296
New Antibiotics with Novel Mode of Action
302
162 Antibiotics with Novel Mode of Action from Old Classes?
303
163 Approaches that Target the Resistance Mechanism Itself
305
164 New Antibacterial Targets
306
165 Conclusion
309
Synthetic Combinatorial Libraries A New Tool for Antimicrobial Agent Discovery
311
1722 Peptide SCL Generation
312
1723 Strategies for the Identification of Active Peptides from an SCL
313
173 Antimicrobial Peptides Derived from SCLs
315
175 Conclusions
317
Strobilurins and Oudemansins
320
183 Biological Activities Mode of Action
322
184 Syntheses of Strobilurins and Oudemansins
323
185 Structural Requirements for the Antifungal Activities
329
References
332
Subject Index
335
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