Contemporary Chemical Approaches for Green and Sustainable Drugs (Advances in Green Chemistry)

Contemporary Chemical Approaches for Green and Sustainable Drugs provides readers with the knowledge they need to integrate sustainable approaches into their work. Sections cover different aspects of green and sustainable drug development from design to disposal, including computer-aided drug design, green resourcing of drugs and drug candidates, an overview of the health concerns of pharmaceutical pollution, and a survey of potential chemical methods for its reduction. Drawing together the knowledge of a global team of experts, this book provides an inclusive overview of the chemical tools and approaches available for minimizing the negative environmental impact of current and newly developed drugs. This will be a useful guide for all academic and industrial researchers across green and sustainable chemistry, medicinal chemistry, environmental chemistry and pharmaceutical science. Provides an integrative overview of the environmental risks of drugs and drug by products to support chemists in pre-emptively addressing these issues. Highlights the advantages of computer-aided drug design, green and sustainable sourcing, and novel methods for the production of safer, more effective drugs. Presents individual chapters written by renowned experts with diverse backgrounds. Reflects research in practice through selected case studies and extensive state-of-the-art reference sections to serve as a starting point in the design of any specialized environmentally-conscious medicinal chemistry project. Cover Half Title 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 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Cover back The Design, Discovery, Development And Use Of Medicinal Agents Produces A Whole Range Of Environmental Contaminants Which Have A Damaging Ecological Impact. By Acknowledging And Addressing These Issues, Chemists Can Take Preventative Steps At Multiple Stages In The Process, From Using Computational Models And Selecting Green Solvents, To Designing For Degradation And Creating New Remediation Tools. Contemporary Chemical Approaches For Green And Sustainable Drugs Provides Readers With The Knowledge They Need To Integrate Such Sustainable Approaches Into Their Work. After An Introduction To The Major Focus Areas In The Field, The Book Includes Four Parts, Each Dealing With Different Aspects Of Green And Sustainable Drug Development From Design To Disposal. These Include Computer-aided Drug Design, Green Resourcing Of Drugs And Drug Candidates, An Overview Of The Health Concerns Of Pharmaceutical Pollution, And A Survey Of Potential Chemical Methods For Its Reduction. Drawing Together The Knowledge Of A Global Team Of Experts, Contemporary Chemical Approaches For Green And Sustainable Drugs Provides An Inclusive Overview Of The Chemical Tools And Approaches Available For Minimizing The Negative Environmental Impact Of Current And Newly Developed Drugs, Making It A Useful Guide For All Academic And Industrial Researchers Across Green And Sustainable Chemistry, Medicinal Chemistry, Environmental Chemistry And Pharmaceutical Science. Provides An Integrative Overview Of The Environmental Risks Of Drugs And Drug By Products To Support Chemists In Pre-emptively Addressing These Issues Highlights The Advantages Of Computer-aided Drug Design, Green And Sustainable Sourcing, And Novel Methods For The Production Of Safer, More Effective Drugs Presents Individual Chapters Written By Renowned Experts With Diverse Backgrounds Reflects Research In Practise Through Selected Case Studies And Extensive State-of-the-art Reference Sections To Serve As A Starting Point In The Design Of Any Specialized Environmentally-conscious Medicinal Chemistry Project