مولکول‌های کوچک بیولوژیک فعال: کاربردهای مدرن و چشم‌اندازهای درمانی

"Biologically Active Small Molecules: Modern Applications and Therapeutic Perspectives focuses on small molecules as active pharmacological agents, their pharmacotherapeutically active properties, new approaches in drug discovery using small molecules, and biopharmaceutic approaches for low molecular weight ligands. Molecules of low mass play a pivotal role in pharmacology because they exhibit multifarious pharmacological effects. Small molecules have become universally popular due to their simple chemistry, easy separation techniques, versatile acceptance for computational studies, large number of places for the substitution of active chemical moieties by well-established synthetic routes with less effort, better quality attributes, and ability to demonstrate numerous biological activities. This book provides a multidisciplinary approach that delivers the most updated knowledge and advances of some newly developed therapeutically active low molecular weight compounds. It includes chapters that present up-to-date and concise content on the classification, structures, chemical syntheses, medicinal chemistry, pharmacology, biochemical pathways, mechanism of actions, side effects, and adverse effects of small molecule drug discovery. The book covers a broad area by highlighting the advances of inter- and multidisciplinary fields of medicine, chemical sciences, and pharmaceuticals. The flowcharts, figures, illustrations, and diagrams provide important information and will be of great interest for readers."-- Provided by publisher Cover Half Title Biologically Active Small Molecules: Modern Applications and Therapeutic Perspectives Copyright About the Editors Contents Contributors Abbreviations Foreword Preface Part I: Small Molecules as Active Pharmacological Agents 1. Bedaquiline: The New Antituberculosis Drug on the Horizon ABSTACT 1.1 INTRODUCTION 1.2 PHARMACOLOGY 1.3 DRUG–DRUG INTERACTION 1.4 SAFETY 1.5 ISSUES OF DRUG RESISTANCE 1.6 THE CURRENT CHALLENGES AND WAY FORWARD WITH BEDAQUILINE 1.7 CONCLUSION REFERENCES 2. Plant-Derived Natural Products as Antiglycating Agents 2.1 INTRODUCTION 2.2 DIABETES 2.3 CURRENT TREATMENT OF DIABETES AND ITS COMPLICATIONS 2.4 GLYCATION 2.5 PHARMACOLOGICAL INTERVENTION OF DELETERIOUS REACTIONS 2.6 PREVENTION OF GLYCATION 2.7 NEED FOR NATURAL SOURCES OF INHIBITORS 2.8 ANTIDIABETIC AND ANTIGLYCATING ACTIVITIES IN PLANTS 2.9 INTRINSIC DEFENSE MECHANISMS FOR PREVENTION OF GLYCATION 2.10 BIOCHEMICAL AND ANALYTICAL TECHNIQUES TO STUDY ANTIGLYCATION PROPERTIES 2.11 CONCLUSION ACKNOWLEDGMENT KEYWORDS REFERENCES 3. Perspectives of Chalcone-Based Nf-Κβ Inhibitors as Anti-Inflammatory Agents 3.1 INTRODUCTION 3.2 INFLAMMATORY MEDIATORS 3.3 TREATMENT APPROACHES 3.4 DRUG DESIGN, DISCOVERY, AND DEVELOPMENT 3.5 CHALCONES 3.6 NF-κβ 3.7 CHALCONES AS NF-ΚΒ INHIBITORS 3.8 CONCLUSION KEYWORDS REFERENCES 4. Coronaviruses: Molecular Modeling and Docking Studies of Potential Drug Candidates Showing Anti-Covid-19 Activity ABSTRACT 4.1 INTRODUCTION: THE DISEASE THAT SHOOK THE WORLD IN 2019 4.2 TYPES OF CORONAVIRUS THREATS AND THREATS HUMANITY FROM PAST TO PRESENT 4.3 NOVEL CORONAVIRUS 4.4 CONCLUSION KEYWORDS REFERENCES Part II: Pharmacotherapeutically Active Classes 5. Perspectives on Local Anesthetics in Medicine ABSTRACT 5.1 INTRODUCTION 5.2 NERVE CONDUCTION 5.3 MECHANISM OF ACTION OF LAS 5.4 ESSENTIAL CHEMICAL FEATURES OF LAS 5.5 TYPES OF LOCAL ANASTHETICS 5.6 ADDITIVES TO LAS 5.7 SELECTING LAS FOR PERIPHERAL NERVE BLOCKS 5.8 MIXING OF LAS 5.9 SYSTEMIC TOXICITY OF LAS 5.10 PHARMACODYNAMICS AND TREATMENT OF LA TOXICITY 5.11 TECHNIQUES USED FOR LOCAL ANESTHESIA 5.12 CONCLUSION KEYWORDS REFERENCES 6. Pharmacotherapeutic Perspectives on Adrenergic Agonists ABSTRACT 6.1 CHEMICAL CLASSIFICATION OF ADRENERGIC AGONISTS 6.2 MECHANISM OF NEUROTRANSMISSION AT THE ADRENERGIC NEURON 6.3 ADRENERGIC RECEPTORS 6.4 ADRENERGIC DRUGS (SYMPATHOMIMETICS) 6.5 CONCLUSION KEYWORD REFERENCES 7. Therapeutic Perspectives of Adrenergic Antagonists ABSTRACT 7.1 α-BLOCKERS 7.2 α-ADRENERGIC ANTAGONIST DRUGS 7.3 β-ADRENERGIC ANTAGONIST CLASSIFICATION 7.4 CONCLUSION KEYWORDS REFERENCES 8. Skeletal Muscle Relaxants: Concepts and Developments 8.1 INTRODUCTION 8.2 PRINCIPLES OF NEUROMUSCULAR TRANSMISSION 8.3 CASCADE OF THE SEQUENTIAL EVENTS 8.4 CLASSIFICATION 8.4.1 NEUROMUSCULARBLOCKING DRUGS 8.4.1.1 NONDEPOLARIZING BLOCKERS 8.4.1.2 DEPOLARIZING BLOCKERS 8.4.1.2.1 Mechanism of Action 8.4.1.2.2 Pharmacokinetics 8.4.1.2.3 Therapeutic Applications 8.4.1.2.4 Toxic Effects and Contraindications 8.4.2 CENTRALLY ACTING MUSCLE RELAXANTS 8.4.2.1 CLASSIFICATION 8.4.2.1.1 Mephenesin 8.4.2.1.2 Carisoprodol 8.4.2.1.3 Chlorzoxazone 8.4.2.1.4 Chlormezanone 8.4.2.1.5 Methocarbamol 8.4.2.1.6 Diazepam 8.4.2.1.7 Baclofen 8.4.2.1.8 Cyclobenzaprine 8.4.2.1.9 Tizanidine 8.4.3 DIRECTLY ACTING SKELETAL MUSCLE RELAXANTS 8.4.3.1 THERAPEUTIC APPLICATION 8.4.3.2 UNDESIRED EFFECTS 8.4.4 MISCELLANEOUS AGENTS 8.4.4.1 MOTOR NERVE BLOCKER 8.5 CONCLUSION KEYWORDS REFERENCES 9. Nonsteroidal Anti-Inflammatory Drugs: Concepts and Innovations ABSTRACT 9.1 INTRODUCTION 9.2 CLASSIFICATION OF NSAIDS2 9.2.1 ON THE BASIS OF MECHANISM OF ACTION 9.2.2 ON THE BASIS OF CHEMICAL FORMULA 9.3 PHARMACOLOGICAL EFFECTS OF NSAIDS3 9.3.1 ANTI-INFLAMMATORY EFFECTS OF NSAIDS 9.3.2 ANALGESIC EFFECTS OF NSAIDS 9.3.3 ANTIPYRESIS EFFECTS OF NSAIDS 9.3.4 ANTIPLATELET AGGREGATORY EFFECTS OF NSAIDS 9.3.5 ANAPHYLACTOID ACTIONS OF NSAIDS 9.4 DRUG INTERACTIONS4 9.4.1 PHARMACODYNAMIC INTERACTION OF NSAIDS WITH OTHER DRUGS 9.4.2 PHARMACOKINETIC INTERACTION OF NSAIDS WITH OTHER DRUGS 9.5 CONTRAINDICATIONS5 9.6 ADVERSE EFFECTS6 9.6.1 CARDIOVASCULAR 9.6.2 GASTROINTESTINAL 9.6.3 INFLAMMATORY BOWEL DISEASE 9.6.4 RENAL 9.6.5 PREGNANCY 9.6.6 PHOTOSENSITIVITY 9.6.7 OTHERS 9.7 MECHANISM OF ACTION7 9.8 PHARMACOKINETICS8 9.9 ASPIRIN9 9.9.1 IMPORTANT INFORMATION 9.9.2 PHARMACOLOGICAL EFFECTS 9.9.2.1 ANTIPYRETIC, ANALGESIC, AND ANTI-INFLAMMATORY ACTIONS 9.9.2.1.1 Cardiovascular 9.9.2.1.2 Renal 9.9.2.1.3 Gastrointestinal 9.9.2.1.4 Gestation 9.9.2.1.5 Respiratory system 9.9.3 PHARMACOKINETICS 9.9.4 DOSAGE AND ADMINISTRATION 9.9.5 PRECAUTIONS 9.9.6 ADVERSE REACTIONS 9.9.7 SYMPTOMS AND TREATMENT OF OVERDOSE 9.9.8 INDICATIONS AND CLINICAL USES 9.10 CELECOXIB10 9.10.1 PHARMACOLOGICAL EFFECTS 9.10.2 PHARMACOKINETICS 9.10.3 PRECAUTIONS 9.10.4 CONTRAINDICATIONS 9.10.5 ADVERSE EFFECTS 9.10.6 INTERACTIONS 9.10.7 DOSAGE AND ADMINISTRATION 9.11 DICLOFENAC11 9.11.1 PHARMACOLOGICAL EFFECTS 9.11.2 PHARMACOKINETICS 9.11.3 PRECAUTIONS 9.11.4 CONTRAINDICATIONS 9.11.5 INTERACTIONS 9.11.6 ADVERSE EFFECTS 9.11.7 DOSAGE AND ADMINISTRATION 9.12 DICLOFENAC POTASSIUM12 9.13 DICLOFENAC SODIUM/MISOPROSTOL13 9.14 DIFLUNISAL14 9.15 ETODOLAC15 9.16 FENOPROFEN16 9.17 FLURBIPROFEN17 9.18 IBUPROFEN18 9.19 INDOMETHACIN19 9.20 KETOPROFEN20 9.21 MAGNESIUM SALICYLATE21 9.22 MECLOFENAMATE SODIUM22 9.23 MEFENAMIC ACID23 9.23.1 IMPORTANT INFORMATIONS 9.23.2 PHARMACOLOGICAL EFFECTS 9.23.3 ADVERSE REACTIONS 9.23.4 PHARMACOLOGICAL USES 9.24 MELOXICAM24 9.24.1 IMPORTANT INFORMATION 9.24.2 PHARMACOLOGICAL EFFECTS 9.24.3 SIDE EFFECTS 9.24.4 PHARMACOLOGICAL USES 9.24.5 DOSAGE AND ADMINISTRATION 9.25 NABUMETONE25 9.26 OXAPROZIN26 9.27 PIROXICAM27 9.28 ROFECOXIB28 9.29 SULINDAC29 9.30 TOLMETIN SODIUM30 9.31 VALDECOXIB31 9.32 SALSALATE32 9.33 NAPROXEN33 9.33.1 ADVERSE EFFECTS KEYWORDS REFERENCES Part III: Modern Approaches in Small Molecule Drug Discovery 10. Biological Databases: Tool for Low Molecular Weight Ligand Discovery Process ABSTRACT 10.1 INTRODUCTION 10.2 BIOLOGICAL DATABASES 10.3 META-DATABASES 10.4 NUCLEIC ACID DATABASES 10.5 AMINO ACID/PROTEIN DATABASES 10.6 ADDITIONAL DATABASES 10.7 CONCLUSION KEYWORDS REFERENCES 11. High-Throughput Screening Technique: Role in the Drug Discovery of Low Molecular Weight Ligands 11.1 INTRODUCTION 11.2 ASSAY DESIGN 11.3 REAGENTS IN HTS 11.4 HITS AND HIT RATES 11.5 AUTOMATIC METHODS OF LIBRARY GENERATION AND ROBOTICS IN HTS 11.6 PROFILING 11.7 SCREENING EXPENSE AND OUTSOURCING SCREENING 11.8 CONCLUSION KEYWORDS REFERENCES 12. Homology Modeling: Applications in the Low Molecular Weight Ligand Designing 12.1 INTRODUCTION 12.2 STEPS INVOLVED IN HOMOLOGY MODELING 12.3 CONCLUSION KEYWORDS REFERENCES Part IV Biopharmaceutics Approaches for Low Molecular Weight Ligands 13. Drug Metabolism: Detoxification and Xenobiotic Biotransformation ABSTRACT 13.1 INTRODUCTION 13.2 PHASE-I AND PHASE-II METABOLISM PATHWAYS 13.3 NOMENCLATURE AND CLASSIFICATION OF CYP AND UGT ENZYMES 13.4 CYP-MEDIATED CATALYTIC BIOTRANSFORMATION REACTIONS 13.5 TISSUE-SPECIFIC DRUG METABOLISM 13.6 PHARMACOLOGICAL AND TOXICOLOGICAL EFFECTS OF METABOLISM/OUTCOMES OF DRUG METABOLISM 13.7 SUBSTRATES OF CYP ENZYMES 13.8 SUBSTRATES OF PHASE-II ENZYMES 13.9 PHASE-I REACTIONS 13.10 PHASE-II REACTIONS 13.11 REGULATION OF CYP EXPRESSION 13.12 REGULATION OF UGT EXPRESSION 13.13 INHIBITION OF CYP AND UGT ACTIVITIES 13.14 FACTORS AFFECTING DRUG METABOLISM 13.15 DRUG–DRUG INTERACTIONS/HERB–DRUG INTERACTIONS FROM ALTERED DRUG METABOLISM 13.16 CONCLUSION KEYWORDS REFERENCES 14. Drug Interactions: Highlights of Adverse Effects of Low Molecular Weight Ligands 14.1 INTRODUCTION 14.2 DRUG–DRUG INTERACTION 14.3 DRUG–FOOD INTERACTIONS 14.4 DRUG–DISEASE INTERACTIONS 14.5 PHYSICAL INTERACTIONS 14.6 CHEMICAL INTERACTIONS 14.7 PHARMACOKINETIC INTERACTIONS 14.8 PHARMACODYNAMIC INTERACTIONS 14.9 INTERACTIONS AT BODY SITES 14.10 MISCELLANEOUS PHARMACODYNAMIC INTERACTIONS 10.11 CONCLUSION KEYWORDS REFERENCES Part V: Evaluation Methods for Small Molecules 15. Low Molecular Weight Antioxidant Agents and Model for Their Evaluation ABSTRACT 15.1 INTRODUCTION 15.2 DIFFERENT TYPES OF FREE RADICALS AND THEIR ROLE IN CELLULAR DAMAGE 15.3 SUPEROXIDE DISMUTASES 15.4 MEASUREMENT OF ANTIOXIDANT ACTIVITY 15.5 CONCLUSION KEYWORDS REFERENCES Index Reasonable efforts have been made to publish reliable data and information, but the authors, editors, and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. 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