Chemotherapeutic targets in parasites: contemporary strategies
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Cambridge [u.a.]
Cambridge Univ. Press
2002
|
| Ausgabe: | 1. publ. |
| Schlagworte: | |
| Online-Zugang: | Publisher description Table of contents Inhaltsverzeichnis |
| Beschreibung: | Includes bibliographical references and index |
| Beschreibung: | XIV, 226 S. graph. Darst. |
| ISBN: | 0521620651 |
Internformat
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| 100 | 1 | |a Mansour, Tag E. |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Chemotherapeutic targets in parasites |b contemporary strategies |c Tag E. Mansour |
| 250 | |a 1. publ. | ||
| 264 | 1 | |a Cambridge [u.a.] |b Cambridge Univ. Press |c 2002 | |
| 300 | |a XIV, 226 S. |b graph. Darst. | ||
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| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Includes bibliographical references and index | ||
| 650 | 4 | |a Antiparasitic Agents |x therapeutic use | |
| 650 | 4 | |a Antiparasitic agents | |
| 650 | 4 | |a Parasites | |
| 650 | 4 | |a Parasitic Diseases |x drug therapy | |
| 650 | 4 | |a Parasitic diseases |x Chemotherapy | |
| 650 | 0 | 7 | |a Chemotherapeutikum |0 (DE-588)4009895-3 |2 gnd |9 rswk-swf |
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Datensatz im Suchindex
| _version_ | 1804129299301662720 |
|---|---|
| adam_text | Contents
Preface page xi
Acknowledgments xiv
1 The Search for Antiparasitic Agents 1
Early Beginnings of Chemotherapy 1
Paul Ehrlich and the Principle of Selective Toxicity 2
Rational Discovery of Antiparasitic Agents 3
Biology of Parasites 4
Biochemical Adaptation of Parasites to the Host 5
Drug Receptor Selectivity 6
Metabolic Pathways as Targets 7
Empirical Screening of Antiparasitic Agents 8
Use of Animal Models in Screening 9
Use of in vitro Parasite Cultures for Screening 9
Designing Chemicals for Selective Targets 12
Relationship between Chemical Structure and Biological
Activity of Inhibitors 13
Quantitative Structure Activity Relationship 13
Combinatorial Technology in Drug Discovery 14
References 16
2 Biophysical, Genomic, and Proteomic Analysis of Drug Targets 19
Biophysical Techniques for Studying Drug Targets 19
X Ray Crystallography 19
Nuclear Magnetic Resonance 20
Use of Recombinant DNA Technology for Studies on Drug Targets 22
Identification of Potential Drug Targets and Candidate Antigens
for Vaccines Using Expressed Sequence Tags 23
V
vi Contents
Genomic Analysis of Parasitic Helminths 24
Caenorhabditis elegans Genome 25
Genome Analysis of Trypanosomatids 25
Genome Analysis of Plasmodiumfalciparum 26
Structural Genomics 27
Proteomics 28
References 30
3 Energy Metabolism in Parasitic Helminths: Targets
for Antiparasitic Agents 33
Life Cycles of Representative Helminths 33
Schistosomes (Blood Flukes) 34
The Liver Fluke Fasciola hepatica 34
The Intestinal Nematode Ascaris suum 34
Energy Metabolism of S. mansoni 35
Glucose Transporters 36
The Glycolytic Pathway 37
Inhibition of Glucose Utilization 39
Phosphofructokinase (PFK) 40
Regulation of PFK 40
Activation of PFK and Glycolysis by Serotonin 41
PFK as a Target for Antischistosomal Antimonials 44
Enzymes Involved in Phosphoenolpyruvate Metabolism 46
Mitochondrial Anaerobic Energy Generating Pathways
in Helminths 46
Phosphoenolpyruvate Carboxykinase (PEPCK) 49
Fumarate Reductase 49
Pyruvate Dehydrogenase Complex (PDC) 49
Anaerobic Mitochondrial Metabolism as Possible Targets
for Antiparasitic Agents 50
References 54
4 Antimalarial Agents and Their Targets 58
Quinine and Quinidine 60
Chloroquine 61
Concentration of Chloroquine in Plasmodium
Food Vacuoles 62
Heme Polymerization: A Target for Chloroquine Action 63
The Proteases of Hemoglobin Digestion 64
Resistance to Chloroquine 70
Contents vii
Antimalarials Used against Chloroquine Resistant Malaria 74
Halofantrine and Mefloquine 74
Artemisinin (Qinghaosu) 74
Quinine 76
Primaquine 76
Antifolates and Their Targets 77
Dihydropteroate Synthase 77
Dihydrofolate Reductase Thymidylate Synthase (DHFR TS) 80
Malaria Resistance to Pyrimethamine 82
Proteases and Merozoite Entrance and Exit from Erythrocytes 83
Antisense Oligodeoxynucleotides 84
References 86
5 Antitrypanosomal and Antileishmanial Targets 90
Tripanothione and Tripanothione Reductase in Protozoa 91
Trypanothione Reductase as a Target for Drug Design 93
Biosynthesis of Trypanothione 93
Effect of Antitrypanosomal Agents on the Trypanothione System 94
Inhibition of Trypanothione Reductase from Leishmania
by Trivalent Antimonials 96
Tryparedoxins 97
Antiprotozoal Effects of Nifurtimox 97
Polyamines and Ornithine Decarboxylase 98
Ornithine Decarboxylase Inhibitors as Antiparasitic Agents 99
Glycolysis: A Target for Antitrypanosomal Agents 101
The Glycosome 101
Glucose Transporters 104
Pyruvate Transporters 104
a Glycerophosphate Oxidase 105
Other Glycolytic Targets 105
Suramin and Glycolysis 106
Melarsoprol 107
Mitochondrial DNA as a Target for Antitrypanosomal Agents 107
Purine and Pyrimidine Metabolism as Targets 108
Purine Salvage Pathways 109
Nucleoside Transporters 111
Nucleoside Ribohydrolases 112
Purine Analogs as Antiparasitic Agents 112
Pyrimidine Metabolism Pathways as Possible Targets 115
Pteridin Reductase in Leishmania major as a Target 116
viii Contents
Antigenic Variation in African Trypanosomes and the Design
of Antiparasitic Agents 117
Protein Farnesylation as a Drug Target 119
Cysteine Proteases as Targets for Antitrypanosomal
and Antileishmanial Agents 120
References 122
6 Targets in Amitochondrial Protists 129
Biology of Amitochondrial Protists 129
Entamoeba histolytica 130
Giardia intestinalis (G. duodenalis) 130
Tricbomonas vaginalis 131
Carbohydrate Metabolism of Entamoeba histolytica 131
Energy Metabolism of Giardia intestinalis 134
Hydrogenosomes and Energy Metabolism in Trichomonads 135
Pyruvate:Ferredoxin Oxidoreductase 137
Mechanism of Antiprotozoal Effects of Metronidazole
and Related 5 Nitroimidazoles 138
Resistance to Metronidazole 141
Potentials for New Drug Targets 143
Pyrophosphate Kinases 143
Alcohol Dehydrogenases and Identification of Antiparasitic
Drugs by Complementation of E. coli Mutants 146
PFOR as a Target 147
Proteinases as Targets 148
References 150
7 Neuromuscular Structures and Microtubules as Targets 156
Neuromuscular Physiology of Nematodes 156
Nicotinic Acetylcholine Receptors (nAChRs) 157
Nicotinic Acetylcholine Receptors in Nematodes 158
y Amino Butyric Acid (GABA) 163
The Action of Piperazine (Diethylenediamine) on GABA Receptors 164
Glutamate as a Neurotransmitter in Nematodes 164
Action of Avermectins on Glutamate Gated Chloride Channels 165
Glutamate Receptors in the Pharynx of Nematodes 167
Bioamine Receptors in Nematodes 169
Microtubules as a Target for Benzimidazoles in Nematodes 170
Antimicrotubule Drugs 171
Benzimidazoles as Anthelmintics 173
Resistance to Benzimidazoles 173
Contents ix
Neuroactive Peptides in Nematodes 174
The Neuromuscular System of Flatworms 175
Evaluation of Motility of Flatworms 176
5 Hydroxytryptamine (Serotonin) in Parasitic Flatworms 176
Cholinergic Systems in Flatworms 178
Influence of Parasite Motility on Parasite Location in the Host 178
Anthelmintics That Act on Motility in Platyhelminths 180
Neuropeptides in Flatworms 180
Potential Research on Anthelmintics 181
References 183
8 Targets in the Tegument of Flatworms 189
Structure and Function of Schistosome Tegument 189
Some Proteins Identified in Schistosome Tegument 192
Protein Attachment to the Tegument 193
Glucose Transport across the Tegument 194
Tegumental Acetylcholine Receptors, Acetylcholinesterase,
and Glucose Uptake by Schistosomes 196
Metrifonate (Bilarcil) as AChE Inhibitor
and Antischistosomal Agent 197
Potential Studies on Tegumental Nicotinic Targets 198
Praziquantel (PZQ) 199
Mechanism of Action of Praziquantel 199
Antigens That Attract the Host s Immune System 201
Resistance of Schistosomes to PZQ^ 202
Potential Studies on Ca2+ Influx across the Tegument 204
Oxamniquine 205
Dyneins in Schistosoma mansoni 206
The Effect of Triclabendazole on Fasciola hepatica Tegument 207
Drugs Acting on the Tegument of Cestodes (Tapeworms) 208
References 209
Epilogue 215
References 219
Index 221
|
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| indexdate | 2024-07-09T19:02:56Z |
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| spelling | Mansour, Tag E. Verfasser aut Chemotherapeutic targets in parasites contemporary strategies Tag E. Mansour 1. publ. Cambridge [u.a.] Cambridge Univ. Press 2002 XIV, 226 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier Includes bibliographical references and index Antiparasitic Agents therapeutic use Antiparasitic agents Parasites Parasitic Diseases drug therapy Parasitic diseases Chemotherapy Chemotherapeutikum (DE-588)4009895-3 gnd rswk-swf Antiparasitäres Mittel (DE-588)4219802-1 gnd rswk-swf Antiparasitäres Mittel (DE-588)4219802-1 s Chemotherapeutikum (DE-588)4009895-3 s DE-604 http://www.loc.gov/catdir/description/cam022/2002067057.html Publisher description http://www.loc.gov/catdir/toc/cam025/2002067057.html Table of contents HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009875970&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Mansour, Tag E. Chemotherapeutic targets in parasites contemporary strategies Antiparasitic Agents therapeutic use Antiparasitic agents Parasites Parasitic Diseases drug therapy Parasitic diseases Chemotherapy Chemotherapeutikum (DE-588)4009895-3 gnd Antiparasitäres Mittel (DE-588)4219802-1 gnd |
| subject_GND | (DE-588)4009895-3 (DE-588)4219802-1 |
| title | Chemotherapeutic targets in parasites contemporary strategies |
| title_auth | Chemotherapeutic targets in parasites contemporary strategies |
| title_exact_search | Chemotherapeutic targets in parasites contemporary strategies |
| title_full | Chemotherapeutic targets in parasites contemporary strategies Tag E. Mansour |
| title_fullStr | Chemotherapeutic targets in parasites contemporary strategies Tag E. Mansour |
| title_full_unstemmed | Chemotherapeutic targets in parasites contemporary strategies Tag E. Mansour |
| title_short | Chemotherapeutic targets in parasites |
| title_sort | chemotherapeutic targets in parasites contemporary strategies |
| title_sub | contemporary strategies |
| topic | Antiparasitic Agents therapeutic use Antiparasitic agents Parasites Parasitic Diseases drug therapy Parasitic diseases Chemotherapy Chemotherapeutikum (DE-588)4009895-3 gnd Antiparasitäres Mittel (DE-588)4219802-1 gnd |
| topic_facet | Antiparasitic Agents therapeutic use Antiparasitic agents Parasites Parasitic Diseases drug therapy Parasitic diseases Chemotherapy Chemotherapeutikum Antiparasitäres Mittel |
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