Contemporary Chemical Approaches for Green and Sustainable Drugs

Front Cover
Contemporary Chemical Approaches for Green and Sustainable Drugs
Contemporary Chemical Approaches for Green and Sustainable Drugs
Copyright
Contents
List of contributors
1 - Using the zebrafish model system to identify the health effects of pharmaceutical pollutants
1. Introduction
2. The zebrafish model system
3. Use of the zebrafish model system in drug discovery
4. Significance of pharmaceutical pollution
5. Use of the zebrafish model system to assess pharmaceutical pollutant toxicity
6. Methods and approaches to assess pharmaceutical pollutant toxicity using the zebrafish model system
6.1 Acute developmental toxicity assessments with the developing zebrafish
6.2 High-throughput screenings (HTS) for developmental toxicity assessments
6.3 Zebrafish developmental and adult behavioral assays to assess pharmaceutical pollutant toxicity
6.4 Cellular and molecular assays to identify mechanisms of pharmaceutical pollutant toxicity
7. Future directions for the use of zebrafish in defining pharmaceutical pollutant toxicity
8. Conclusions
Acknowledgments and Funding Sources
References
2 - Analysis of pharmaceuticals in the environment
1. Introduction
2. Sources of pharmaceutical pollutants
2.1 Effects of trace level pharmaceutical pollutants on humans
2.2 Effects of trace level pharmaceutical pollutants on aquatic environments
3. Analytical methods for trace level analysis of water samples
3.1 Solid phase extraction (SPE)
3.2 High-performance liquid chromatography (HPLC)
3.3 Mass spectrometry (MS)
3.4 Other techniques
4. Risk management
5. Conclusion
List of abbreviations
References
3 - Leaking of antibiotics in the aquatic environment
1. Introduction
2. How antibiotics are reaching the aquatic environment?
2.1 From human use
2.2 From hospital waste
2.2.1 Characterization of hospital waste/effluents
2.3 From animal use
2.4 From agricultural use
2.5 From pharmaceutical industry waste
3. Fate of antibiotics in aquatic environment
4. Conclusion
References
4 - Advances in drug development with the application of artificial intelligence
1. Machine learning and artificial intelligence in the pharmaceutical industry: perspective
2. Data mining techniques
2.1 Statistics
2.2 Clustering
2.3 View
2.4 Decision tree
2.5 Neural networks
3. Artificial neural networks (ANN) in property prediction to drug discovery
4. Support vector machines (SVM) in drug discovery and development
5. Conclusion
List of abbreviations
Acknowledgments
References
Further reading
5 - Virtual screening techniques in pharmaceutical research
1. Introduction
2. Structure-based drug design (SBDD)
2.1 Protein structure prediction
2.1.1 Homology modeling
2.1.2 Threading
2.1.3 Ab initio modeling
2.1.4 Artificial intelligence (AI)-based structure prediction
3. Molecular docking
3.1 Search algorithms
3.2 Scoring functions
3.3 Target flexibility
3.4 De novo drug design
3.5 Binding energy estimation
3.6 Machine/deep learning methods in SBVS
3.6.1 Applications of ML/DL methods in SBDD
4. Ligand-based drug discovery (LBDD)
4.1 Similarity searching
4.1.1 Molecular fingerprints
4.1.2 Similarity coefficients
4.1.3 Applications of similarity search methods
4.2 Ligand-based pharmacophore mapping
4.2.1 Applications of ligand-based pharmacophore mapping
4.3 Quantitative structure-activity relationship (QSAR) modeling
4.3.1 Applications of QSAR modeling
5. Summary and perspectives
References
6 - In silico modeling of environmental toxicity of drugs
1. Introduction
2. Pharmaceutical ecotoxicity analysis: general considerations
2.1 Overview of concerns
3. Release of pharmaceuticals to the environment
3.1 The sources of pharmaceuticals pollution to environment
4. Assessment of ecotoxicity of APIs, limitations, and solutions: a data scientist's perspective
5. Current advancement in ecotoxicity modeling of pharmaceuticals
5.1 In silico tools reported in different research articles
6. Online expert systems for ecotoxicity prediction
7. Conclusion
Nomenclature list
Acknowledgments
References
7 - Sustainable separations in pharmaceutical manufacturing
1. Introduction
1.1 Separation concepts in the pharmaceutical industry
1.2 Continuous and automated separation processes
2. Chromatography-based separations
2.1 Sustainable aspects of chromatography
2.2 Toward green chromatographic techniques
2.2.1 Gas chromatography
2.2.2 Capillary electrophoresis
2.2.3 Counter-current chromatography
2.2.4 Supercritical fluid chromatography
2.3 Strategies toward green liquid chromatography
2.4 Relevant industrial applications: case studies
2.4.1 Computer-assisted method development for efficient scale-up of preparative purifications
2.4.2 Alternative solvent system for silica gel chromatography used in medicinal chemistry labs
2.4.3 Integration of supercritical fluid chromatography into drug discovery workflows
2.5 Conclusions
3. Membrane based separations
3.1 Membrane separation in the pharmaceutical industry: a liquid dominant sector
3.2 Organic solvent nanofiltration (OSN)
3.2.1 Solute enrichment and solvent recovery
3.2.2 API purification and degenotoxification
3.2.3 Membrane cascades for enhancing product and solvent recovery
3.2.4 Membrane-assisted catalysis
3.2.5 Macromolecule synthesis and purification
4. Continuous purification processes
4.1 Classification of the continuous flow purification processes
4.2 Continuous crystallization (CC)
4.3 Centrifugal partition chromatography
4.4 Simulated moving bed chromatography
4.5 Comparison of the previously discussed continuous purification methods
5. Forecasting the future of API separations
List of abbreviations
References
8 - Green synthetic methods in drug discovery and development
1. Introduction
2. Catalysis
2.1 Homogeneous catalysis
2.1.1 Homogeneous catalysis by metal complexes
2.1.2 Catalysis by soluble acids and bases
2.1.3 Organocatalysis
2.2 Heterogeneous catalysis
2.2.1 Metal catalysis
2.2.2 Catalysis by solid, nonmetal catalysts: metal oxides, solid acids, and bases
2.2.3 Nanoparticle catalysis
2.2.4 Phase transfer catalysis
2.2.5 Biocatalysis
3. Nontraditional activation methods and energy efficiency of chemical processes
3.1 Microwave-assisted organic synthesis
3.2 Ultrasonic activation
3.3 Photochemical activation
3.4 Electrochemical activation
4. Conclusions
References
9 - Characterizing the environmentally benign nature of chemical processes: green chemistry metrics
1. Introduction
2. Emergence of green chemistry
3. Sustainable production of pharmaceuticals and their building blocks: quantitative green metrics to evaluate chemical processes
3.1 Mass-related metrics
3.1.1 Atom economy
3.1.2 The E-factor
3.1.3 Environmental quotient (EQ)
3.1.4 Mass efficiency (ME), reaction mass efficiency (RME), and process mass intensity (PMI)
3.1.5 Solvent intensity
3.2 Energy-related metrics
3.2.1 Total process energy
3.2.1.1 Energy consumption as a factor of mass of products
3.2.1.2 Energy for solvent recovery
3.3 Greenhouse gas emission and ozone creation metrics
3.3.1 Total mass of greenhouse gas from energy (as kg of CO2 equivalent)
3.3.2 Photochemical ozone creation potential (POCP)
3.4 Solvent-related metrics
3.4.1 Number of different solvents
3.4.2 Overall estimated recovery efficiency
3.5 Life cycle assessment (LCA)
4. Conclusions
References
10 - Green chemistry approaches to drugs that treat epidemic and pandemic diseases
1. Introduction
2. Antibacterial drugs
2.1 Penicillin and cephalosporin antibiotics
2.2 Macrolide antibiotics
2.2.1 Clarithromycin
2.2.2 Azithromycin
2.3 Fluoroquinolone antibiotics: ciprofloxacin
3. Drugs to treat malaria
3.1 Amodaquine
3.2 Arteminisin
3.3 Hydroxychloroquine
3.4 Piperaquine
4. Drugs to treat HIV/AIDS
4.1 Nevirapine
4.2 Dolutegravir
5. Antivirals to treat COVID-19
5.1 Remdesivir
5.2 Molnupiravir (EIDD-2801, MK-4482)
6. Conclusions
References
Further reading
11 - Dynamic effects of organic molecules for drug delivery in micelles
1. Introduction
2. Drug solubilization through drug delivery vehicles
2.1 Micelles
2.2 Liposomes
3. Molecular drug delivery by organized self-assemblies
3.1 Small molecule-surfactant based drug delivery
3.2 Liposomal system as drug delivery vehicle
3.3 Reverse micelles nanocarriers for drug delivery
4. Conclusion
List of abbreviations
References
12 - Antibody-drug conjugates for targeted delivery
1. Introduction
1.1 What is an antibody-drug conjugate?
1.2 Importance of ADCs in targeted drug delivery
1.3 Current ADCs approved or in clinical trials
2. Composition
2.1 Target and antibody
2.2 Linkers
2.2.1 Cleavable linkers
2.2.1.1 Chemically cleavable linkers
2.2.1.2 Enzyme cleavable linkers
2.2.2 Noncleavable linkers
2.3 Payloads
2.3.1 Tubulin polymerization inhibitors
2.3.2 DNA strand breaker agents
3. Antibody-drug conjugation
3.1 Through side chain lysine residue
3.2 Through side chain cysteine residue
3.3 Drug antibody ratio (DAR)
3.4 Site-specific conjugation
4. Physical stability of antibody-drug conjugates
5. Chemical stability of antibody-drug conjugate
6. Formulation development of antibody-drug conjugate
7. Future aspects of ADCs
List of abbreviations
References
13 - Toward the green synthesis of peptides and peptidic drugs
1. Peptides and peptide synthesis: the formation of peptide bond
1.1 Historical perspective of solution phase peptide synthesis
1.2 Solid-phase peptide synthesis (SPPS)
1.3 Solid-phase fragment/segment condensation in the 1980s
1.4 Automatization of the SPPS
2. Improvements in the solid-phase method
2.1 Optimization of the linkers and polymeric supports in SPPS
2.2 Development of the N-terminal amino protecting groups
2.3 On resin monitoring of the coupling efficiency
2.4 Development of coupling agents and coupling methodologies
3. Novel methods for dissolving limitations of SPPS
3.1 Native chemical ligation (NCL)
3.2 Continuous-flow solid-phase peptide synthesis (CF-SPPS)
3.3 Solution-phase continuous-flow peptide synthesis
3.4 Microwave-assisted peptide synthesis
4. Large-scale peptide synthesis methods
4.1 Continuous-flow large scale peptide synthesis
4.2 Solution-phase large-scale peptide synthesis
4.3 Solid-phase large-scale peptide synthesis
4.4 Hybrid large-scale peptide synthesis
5. Green chemistry aspects of peptide synthesis
6. Summary
List of abbreviations
Acknowledgments
References
14 - The multitarget approach as a green tool in medicinal chemistry
1. Introduction
2. The green impact of multitarget drug discovery
2.1 Green syntheses in multitarget drug development (MTDD)
2.2 Combining in silico and experimental methods: inherently green improvement to design and testing efficiency
3. Multitarget lead generation—screening-versus knowledge-based approaches
3.1 Knowledge-based rational design
3.2 Screening-based multitarget lead generation
3.2.1 Advancements in computational multitarget drug design
3.3 Natural product-inspired scaffolds for designing MTDs
4. Selected case studies with multitarget focus
4.1 Neurodegenerative diseases—Alzheimer's disease
4.2 Infectious diseases
4.3 Cancer
4.4 Epigenetic polypharmacology
5. Challenges and limitations in multitarget drug design and development
6. Conclusions
List of abbreviations
References
15 - Directed evolution: a new powerful tool in drug development
1. Introduction
2. Methods in directed evolution
2.1 Methods for gene manipulation
2.1.1 Error-prone PCR
2.1.2 Sequence saturation mutagenesis (SeSaM)
2.1.3 Site-directed mutagenesis
2.1.4 Cassette mutagenesis
2.1.5 DNA shuffling
2.1.6 Iterative saturation mutagenesis
2.1.7 Staggered extension process (StEP)
2.1.8 Incremental truncation for the creation of hybrid enzymes (ITCHY)
2.1.9 Random chimeragenesis on transient templates (RACHITT)
2.1.10 Nucleotide exchange and excision technology (NExT)
2.2 Methods for screening and selection of enzyme libraries
2.2.1 Agar plate assays
2.2.2 Microtiter plate assays
2.2.3 Microfluidic assays
2.2.4 Förster resonance energy transfer (FRET)
3. Application of directed evolution in drug development
3.1 Simvastatin synthase LovD
3.2 Transaminase ATA-17 in the synthesis of sitagliptin
3.3 Candida antarctica lipase A (CALA) in the synthesis of ibuprofen
4. Perspectives
List of abbreviations
References
16 - Conventional and advanced treatment methods for the removal of pharmaceuticals and related compounds in wastewater
1. Introduction
2. Overview of conventional wastewater treatment
3. Effectiveness of conventional wastewater treatment in removing pharmaceuticals
4. Advanced treatment processes for the removal of pharmaceuticals from municipal wastewater
4.1 Overview
4.2 Ozonation
4.3 Activated carbon methods
4.4 Membrane-based technologies
4.4.1 Membrane filtration methods
4.4.2 Membrane bioreactor (MBR) methods
4.5 Newer methods: advanced oxidative processes
4.5.1 Overview
4.5.2 UV photolysis
4.5.3 UV with other oxidizing agents
4.5.4 Homogeneous photocatalysis with Fenton reagent
5. Case Study #1: San Bernardino municipal water department
5.1 Rapid infiltration and extraction (RIX) facility
5.1.1 Prospective methods
5.1.1.1 Heterogeneous photocatalysis
5.1.1.2 Moving bed biofilm reactors
5.1.1.3 Electrochemical oxidation
5.1.1.4 Hybrid methods
6. Case Study #2: the Orange County Sanitation District, Fountain Valley, CA
6.1 Ground water replenishment system (GWRS)
7. Conclusion
References
Further reading
Index
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