Contemporary Chemical Approaches for Green and Sustainable Drugs

566 Pages·2022·14.154 MB·english

by  Török M. (ed.)

Contemporary Chemical Approaches
for Green and Sustainable Drugs
Advances in Green and
Sustainable Chemistry
Contemporary
Chemical Approaches
for Green and
Sustainable Drugs
Series Editor
Be´la To¨ro¨k
Timothy Dransfield
Edited by
Marianna To¨ro¨k
Elsevier
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Contents
List ofcontributors xiii
1. Using the zebrafish model system to identify the
health effects of pharmaceutical pollutants
Christina Kaucic,AnushaLakshmiDharmavathi
andJenniferL.Freeman
1. Introduction 1
2. Thezebrafishmodelsystem 2
3. Useofthezebrafishmodelsystemindrugdiscovery 3
4. Significanceofpharmaceuticalpollution 6
5. Useofthezebrafishmodelsystemtoassesspharmaceutical
pollutanttoxicity 7
6. Methodsandapproaches toassesspharmaceuticalpollutant
toxicityusingthezebrafishmodelsystem 13
6.1 Acutedevelopmentaltoxicityassessmentswiththe
developingzebrafish 13
6.2 High-throughputscreenings(HTS)fordevelopmentaltoxicity
assessments 14
6.3 Zebrafishdevelopmentalandadultbehavioralassaystoassess
pharmaceuticalpollutant toxicity 16
6.4 Cellularandmolecularassaystoidentifymechanismsof
pharmaceuticalpollutant toxicity 18
7. Futuredirectionsfor theuseofzebrafishindefining
pharmaceuticalpollutanttoxicity 20
8. Conclusions 21
AcknowledgmentsandFundingsources 21
References 21
2. Analysis of pharmaceuticals in the environment
Aditya KulkarniandScottE.Miller
1. Introduction 27
2. Sourcesofpharmaceuticalpollutants 28
2.1 Effectsoftracelevelpharmaceuticalpollutantson
humans 29
2.2 Effectsoftracelevelpharmaceuticalpollutantson
aquaticenvironments 30
v
vi Contents
3. Analyticalmethods for tracelevelanalysisofwatersamples 32
3.1 Solidphaseextraction(SPE) 33
3.2 High-performanceliquidchromatography(HPLC) 35
3.3 Massspectrometry(MS) 36
3.4 Othertechniques 39
4. Riskmanagement 41
5. Conclusion 41
Listofabbreviations 41
References 42
3. Leaking of antibiotics in the aquatic environment
Indu,ManishaSharmaandKashyapKumar Dubey
1. Introduction 47
2. Howantibioticsarereaching theaquaticenvironment? 49
2.1 Fromhumanuse 49
2.2 Fromhospitalwaste 53
2.3 Fromanimaluse 56
2.4 Fromagriculturaluse 58
2.5 Frompharmaceuticalindustrywaste 59
3. Fateofantibioticsinaquatic environment 60
4. Conclusion 61
References 62
4. Advances in drug development with the
application of artificial intelligence
ManuelaSouzaLeite,AndersonAllesdeJesus,
PauloJardelLeiteAraujoandBrunnoFerreiradosSantos
1. Machinelearningandartificialintelligence inthe
pharmaceuticalindustry:perspective 69
2. Datamining techniques 71
2.1 Statistics 72
2.2 Clustering 72
2.3 View 72
2.4 Decisiontree 73
2.5 Neuralnetworks 73
3. Artificialneural networks(ANN)inpropertyprediction
todrugdiscovery 75
4. Supportvectormachines(SVM)indrugdiscoveryand
development 78
5. Conclusion 80
Listofabbreviations 81
Acknowledgments 81
References 81
Further reading 88
Contents vii
5. Virtual screening techniques in pharmaceutical
research
Justine C. Williams, Stanley Opare, Senthil Kumar Sugadoss,
AravindhanGanesanandSubhaKalyaanamoorthy
1. Introduction 89
2. Structure-based drugdesign(SBDD) 91
2.1 Proteinstructureprediction 92
3. Moleculardocking 96
3.1 Searchalgorithms 96
3.2 Scoringfunctions 97
3.3 Targetflexibility 101
3.4 Denovodrugdesign 101
3.5 Binding energyestimation 103
3.6 Machine/deeplearningmethodsinSBVS 104
4. Ligand-based drugdiscovery (LBDD) 107
4.1 Similarity searching 108
4.2 Ligand-basedpharmacophoremapping 113
4.3 Quantitativestructure-activity relationship(QSAR)
modeling 115
5. Summaryandperspectives 117
References 119
6. In silico modeling of environmental toxicity
of drugs
KabiruddinKhanandKunal Roy
1. Introduction 129
2. Pharmaceuticalecotoxicityanalysis: generalconsiderations 129
2.1 Overviewofconcerns 130
3. Releaseofpharmaceuticalstotheenvironment 131
3.1 Thesourcesofpharmaceuticals pollutiontoenvironment 131
4. Assessment ofecotoxicityofAPIs,limitations,andsolutions:
a datascientist’sperspective 131
5. Current advancement inecotoxicitymodeling of
pharmaceuticals 132
5.1 Insilicotoolsreportedindifferentresearcharticles 133
6. Online expertsystemsforecotoxicity prediction 141
7. Conclusion 149
Nomenclaturelist 150
Acknowledgments 151
References 151
viii Contents
7. Sustainable separations in pharmaceutical
manufacturing
GergoIgnacz,RobertOrkenyi,ArpadKonczolandGyorgySzekely
1. Introduction 155
1.1 Separationconceptsinthepharmaceuticalindustry 156
1.2 Continuous andautomatedseparationprocesses 158
2. Chromatography-basedseparations 159
2.1 Sustainableaspectsofchromatography 159
2.2 Towardgreenchromatographictechniques 159
2.3 Strategiestoward greenliquidchromatography 162
2.4 Relevantindustrialapplications:casestudies 166
2.5 Conclusions 167
3. Membranebasedseparations 167
3.1 Membraneseparationinthepharmaceuticalindustry:
a liquiddominantsector 167
3.2 Organicsolventnanofiltration(OSN) 168
4. Continuouspurificationprocesses 174
4.1 Classification ofthecontinuousflowpurification
processes 174
4.2 Continuous crystallization(CC) 175
4.3 Centrifugalpartitionchromatography 177
4.4 Simulated movingbedchromatography 179
4.5 Comparisonofthepreviouslydiscussedcontinuous
purificationmethods 180
5. Forecastingthefuture ofAPI separations 183
Listofabbreviations 184
References 185
8. Green synthetic methods in drug discovery and
development
GuoshuXie,RitaBernadettVlocsko´ andBe´laTo¨ro¨k
1. Introduction 201
2. Catalysis 203
2.1 Homogeneous catalysis 204
2.2 Heterogeneouscatalysis 217
3. Nontraditionalactivationmethodsandenergyefficiencyof
chemicalprocesses 238
3.1 Microwave-assisted organicsynthesis 238
3.2 Ultrasonicactivation 242
3.3 Photochemicalactivation 248
3.4 Electrochemicalactivation 256
4. Conclusions 260
References 261
Contents ix
9. Characterizing the environmentally benign nature of
chemical processes: green chemistry metrics
DavidDaggett,YizhouShi andBe´laTo¨ro¨k
1. Introduction 281
2. Emergence ofgreenchemistry 282
3. Sustainableproductionofpharmaceuticalsandtheirbuilding
blocks: quantitativegreenmetrics toevaluatechemical
processes 282
3.1 Mass-relatedmetrics 283
3.2 Energy-related metrics 294
3.3 Greenhousegasemissionandozonecreationmetrics 296
3.4 Solvent-relatedmetrics 298
3.5 Life cycleassessment(LCA) 300
4. Conclusions 300
References 301
10. Green chemistry approaches to drugs that treat
epidemic and pandemic diseases
BerkeleyW.Cue
1. Introduction 307
2. Antibacterial drugs 309
2.1 Penicillinandcephalosporinantibiotics 309
2.2 Macrolideantibiotics 310
2.3 Fluoroquinoloneantibiotics:ciprofloxacin 313
3. Drugs totreatmalaria 313
3.1 Amodaquine 314
3.2 Arteminisin 315
3.3 Hydroxychloroquine 317
3.4 Piperaquine 318
4. Drugs totreatHIV/AIDS 318
4.1 Nevirapine 319
4.2 Dolutegravir 321
5. Antivirals totreatCOVID-19 322
5.1 Remdesivir 322
5.2 Molnupiravir(EIDD-2801,MK-4482) 323
6. Conclusions 325
References 326
Further reading 330
11. Dynamic effects of organic molecules for drug
delivery in micelles
DebanjanaGhosh,RiaRamoutarandShainazLandge
1. Introduction 333
2. Drugsolubilizationthroughdrugdeliveryvehicles 335
2.1 Micelles 335
2.2 Liposomes 336
x Contents
3. Moleculardrugdeliverybyorganized self-assemblies 337
3.1 Small molecule-surfactantbaseddrugdelivery 337
3.2 Liposomalsystemasdrugdeliveryvehicle 347
3.3 Reversemicellesnanocarriersfordrugdelivery 360
4. Conclusion 370
Listofabbreviations 371
References 373
12. Antibody-drug conjugates for targeted delivery
GarimaPandey,SunilK.TripathiandVivekBulbule
1. Introduction 377
1.1 What isanantibody-drugconjugate? 377
1.2 ImportanceofADCs intargeteddrugdelivery 379
1.3 Current ADCsapprovedorinclinicaltrials 380
2. Composition 385
2.1 Targetandantibody 385
2.2 Linkers 386
2.3 Payloads 395
3. Antibody-drugconjugation 396
3.1 Throughsidechainlysineresidue 397
3.2 Throughsidechaincysteineresidue 398
3.3 Drugantibodyratio(DAR) 400
3.4 Site-specific conjugation 400
4. Physicalstabilityofantibody-drug conjugates 403
5. Chemicalstabilityofantibody-drugconjugate 404
6. Formulationdevelopmentofantibody-drug conjugate 405
7. FutureaspectsofADCs 406
Listofabbreviations 407
References 408
13. Toward the green synthesis of peptides and
peptidic drugs
Do´raBogda´n,LeventeKa´rpa´tiandIstva´nM.Ma´ndity
1. Peptidesandpeptidesynthesis:theformationofpeptide
bond 421
1.1 Historicalperspective ofsolutionphasepeptidesynthesis 421
1.2 Solid-phase peptidesynthesis(SPPS) 422
1.3 Solid-phase fragment/segmentcondensationinthe1980s 424
1.4 AutomatizationoftheSPPS 424
2. Improvements inthe solid-phasemethod 426
2.1 Optimization ofthelinkersandpolymericsupportsin
SPPS 426
2.2 DevelopmentoftheN-terminalaminoprotecting
groups 427
2.3 On resinmonitoring ofthecouplingefficiency 428