Green Approaches in Medicinal Chemistry for Sustainable Drug Design 1st Edition by Bimal Banik 0128175923 9780128175927

Part One: Green chemistry

Chapter 1: Green chemistry assisted synthesis of natural and synthetic compounds as anticancer agent

1.1. Introduction

1.2. Natural products as anticancer agents

1.3. Synthetic compounds as anticancer agents

1.4. Conclusion

References

Chapter 2: Antibacterial and antimicrobial coatings on metal substrates by cold spray technique: Pre

2.1. Introduction

2.2. The need for the development of antibacterial and antimicrobial coatings

2.3. The coating techniques

2.4. Thermal spraying: Processes and techniques

2.5. Cold spray: The process and its advantages

2.6. Present status of the antibacterial and antimicrobial coating by cold spray

2.7. Sustainability and cold spray technique

2.8. Green aspects of cold spray

2.9. Future prospects and concluding remarks

2.10. Summary

References

Chapter 3: Graphene oxide nanosheets as sustainable carbocatalysts: Synthesis of medicinally importa

3.1. Introduction

3.2. Strategies for the synthesis of medicinally important heterocyclic scaffolds using GO and CMGs

3.2.1. Synthesis of substituted pyrroles and related heterocycles using GO nanosheets

3.2.2. Synthetic approaches for quinazoline derivatives

3.2.3. Multicomponent approach for the synthesis of substituted pyridine derivatives

3.2.4. Synthesis of benzothiazines, benzothiazoles, imidazoles, and benzimidazoles

3.2.5. Synthesis of functionalized quinoxalines

3.2.6. Synthesis of 4H-pyrans, coumarins, chromenes, flavones, and xanthenes

3.2.7. Synthesis of pyrimidones

3.2.8. Catalytic processes for the synthesis of 1,2,3-triazoles

References

Chapter 4: Sustainable green technologies for synthesis of potential drugs targeted toward tropical

4.1. Introduction

4.2. Dose reduction through improved drug composition

4.3. Green dose setting

4.4. Reduction of cost through green chemistry

4.5. Green chemistry in ARV therapy

4.6. Green technology in malaria treatment

4.7. Conclusion

References

Chapter 5: Clay-mediated synthesis of biologically active molecules: Green and sustainable approache

5.1. Introduction

5.1.1. Green and sustainable approach

5.1.1.1. Basic principles of green chemistry

5.1.1.2. Basic green methods for chemical synthesis

Microwave-induced method

Sonication method

Biosynthetic method

5.1.2. Clay minerals

5.1.2.1. Classification of clay

5.2. Clay-mediated synthesis of biologically active molecules

5.2.1. Natural clay

5.2.2. Montmorillonite K-10 clay

5.2.3. Modified montmorillonite clay

5.2.4. Modified montmorillonite K-10 clay

5.2.5. Natural bentonite clay

5.2.6. Modified bentonite clay

5.2.7. Montmorillonite KSF clay

5.2.8. Modified montmorillonite KSF clay

5.2.9. Kaolin

5.2.10. Modified kaolin

5.2.11. Pillared clay

5.2.12. Super acid clays

5.2.13. Comparative study of montmorillonite-KSF and K-10 clays

5.3. Conclusions

Acknowledgment

References

Further reading

Chapter 6: The role of ionic liquid in medicinal chemistry

6.1. Introduction

6.1.1. Green chemistry and its requirements

6.1.2. Green and alternative solvents in organic synthesis

6.1.3. ILs and their synthesis

6.1.4. Properties of ILs and their applications in green chemistry

6.1.5. Green applications of ILs in medicinal chemistry

6.2. ILs in synthesis of drugs and drug precursors

6.3. ILs for extraction of bioactive natural products from plants

6.3.1. Extraction of bioactive natural products through ultrasonic-assisted ionic liquid approach

6.3.2. Extraction of bioactive natural products through microwave-assisted ionic liquid approach

6.3.3. IL strategy for the reactive dissolution of biomass to extract natural ingredients

6.4. ILs in the detection of pharmaceutically active compounds

6.5. ILs for pharmaceutical crystallization

6.6. ILs in pharmaceutical purification and separation

6.6.1. Continuous pharmaceutical manufacturing using ILs

6.6.2. Chromatographic purifications using ILs

6.7. Biological activities of ILs

6.7.1. Antimicrobial activities of ILs

6.7.2. Antibiofilm activities of ILs

6.7.3. Antiproliferative profile of ILs

6.8. ILs as APIs

6.8.1. The oligomeric methodology: Stoichiometric to nonstoichiometric API-ILs with protic ion

6.8.2. Prodrug methodology

6.9. Conclusion

References

Chapter 7: Synthesis of medicinally important heterocycles inside the nanoreactors built-in nonconve

7.1. Introduction

7.2. Surfactant and nanodimensional micelle

7.3. Properties and uses of the nanoreactors

7.4. Dehydration reaction in water for syntheses of medicinally important esters, ethers, and thioet

7.5. Cyclization reaction developed inside the nanoreactor to achieve bioactive heterocycles

7.6. Oxidative cyclization

7.7. Multicomponent reaction

7.8. CC bond-forming reactions

7.9. Carbon-heteroatom bond-forming reactions

7.10. Povarov reaction

7.11. Hydrolysis

7.12. Click reaction

7.13. Reduction strategies in water

7.14. Halogenation

7.15. Metal-catalyzed CC bond-forming reaction

7.16. Conclusion

References

Further reading

Chapter 8: Green synthesis of nanoparticles and nanocomposites: Medicinal aspects

8.1. Nanoparticles

8.2. Nanocomposites

8.3. Conclusion

Acknowledgments

References

Part Two: Methods and synthesis

Chapter 9: Use of sustainable organic transformations in the construction of heterocyclic scaffolds

9.1. Introduction

9.2. Organic transformations in deep eutectic solvents

9.2.1. Synthesis of heterocyclic scaffolds

9.2.1.1. Synthesis of pyrroles

9.2.1.2. Synthesis of furans (naphthofurans)

9.2.1.3. Synthesis of thiophenes

9.2.1.4. Synthesis of pyrazoles

9.2.1.5. Synthesis of pyranopyrazoles

9.2.1.6. Synthesis of imidazoles

9.2.1.7. Synthesis of substituted hydantoins

9.2.1.8. Synthesis of isoxazoles

9.2.1.9. Synthesis of oxazoles

9.2.1.10. Synthesis of thiazoles

9.2.1.11. Synthesis of thiazolidin-4-ones

9.2.1.12. Synthesis of triazole derivatives

9.2.1.13. Synthesis of pyridines

9.2.1.14. Synthesis of 1,4-dihydropyridines

9.2.1.15. Synthesis of imidazo[1,2-a]pyridines

9.2.1.16. Synthesis of pyrazolo[3,4-b]pyridines

9.2.1.17. Synthesis of pyrimidines

9.2.1.18. Synthesis of dihydropyrimidines

9.2.1.19. Synthesis of dihydropyrimidinones

9.2.1.20. Synthesis of triazolopyrimidines

9.2.1.21. Synthesis of pyridopyrimidines

9.2.1.22. Synthesis of pyrimidopyrimidinediones

9.2.1.23. Synthesis of chromenothiazolopyrimidinones

9.2.1.24. Synthesis of quinoline derivatives

9.2.1.25. Synthesis of quinazolines

9.2.1.26. Synthesis of acridines

9.2.1.27. Synthesis of naphthyridines

9.2.1.28. Synthesis of pyran derivatives

9.2.1.29. Synthesis of 4H-chromenes

9.2.1.30. Synthesis of xanthenes and tetraketones

9.2.1.31. Synthesis of spirooxindoles

9.2.1.32. Synthesis of seven-membered heterocycles

9.3. Conclusion

References

Chapter 10: One-pot strategy: A highly economical tool in organic synthesis and medicinal chemistry

10.1. Introduction

10.2. One-pot synthesis in carbohydrate chemistry

10.3. One-pot glycosylation strategy in synthesis of medicinally privileged glycosides

10.4. One-pot synthesis of iminosugar

10.5. One-pot synthesis of bioactive heterocycles

10.6. Nitrogen-based bioactive heterocycles

10.7. Regioselective ring opening/ring expansion of chiral aziridine

10.8. N, O, and S-based bioactive heterocycles

10.9. Regioselective oxirane ring opening/expansion

10.10. Regioselective ring opening/expansion of oxetanes

10.11. Synthesis of morpholine/piperazine/thiazine

10.12. Synthesis of functionalized isoxazoles

10.13. Synthesis of polycyclic azaheterocycles

10.14. Synthesis of pyrone derivatives

10.15. Cyclopropane ring expansion

10.16. Synthesis of aza-heterocycles in one-pot ring opening

10.17. Synthesis of oxacyclic heterocycles in one-pot

10.18. Conclusions

Acknowledgments

References

Chapter 11: Organocatalytic cycloaddition reaction: A gateway for molecular complexity

11.1. Introduction

11.2. [4+2] Cycloaddition reaction

11.3. [4+2] Cycloaddition via iminium ion activation

11.4. [4+2] Cycloaddition via enamine activation

11.5. Ox-indoles in the synthesis of spirocyclic indoles

11.6. Conclusions

Acknowledgments

References

Chapter 12: Diverse synthesis of medicinally active steroids

12.1. Background on steroid

12.2. Isolation of steroids molecules

12.2.1. Bachmann´s synthesis of equilenin

12.2.2. Woodward´s synthesis of cholesterol

12.2.3. Synthesis of estrone

12.2.4. Synthesis of cortisone

12.3. Structural classifications, use, and importance

12.3.1. Insect steroids or ecdysteroids

12.3.2. Vertebrate steroids

12.4. Classification based on medicinal properties

12.4.1. Corticosteroids

12.4.2. Plant steroids

12.5. Different classical synthetic methods

12.6. Conclusion

Acknowledgments

References

Further reading

Chapter 13: Reactions in water: Synthesis of biologically active compounds

13.1. Introduction

13.2. Properties of water as solvent in synthesis

13.3. Synthesis of biologically active compounds in water

13.4. Advantage of using water as a solvent [39, 40]

13.5. Limitations of using water as a solvent [41, 42]

13.6. Conclusion

Acknowledgment

References

Chapter 14: Solvent-less reactions: Green and sustainable approaches in medicinal chemistry

14.1. Introduction

14.1.1. Principles of green chemistry

14.1.2. Green chemistry approaches

14.1.2.1. MW technology

14.1.2.2. Ultrasonication

14.1.2.3. Photocatalysis (ultraviolet, visible, and IR irradiation)

14.1.2.4. Grinding technique

14.1.2.5. Milling technique

14.1.3. Experimental conditions for solvent-free reaction

Advantages of solvent-free reaction

Limitations

14.2. Conclusion

Acknowledgment

References

Chapter 15: Versatile thiosugars in medicinal chemistry

15.1. Introduction

15.2. Thiosugars with sulfur as a ring heteroatom: Synthesis and medicinal activity

15.3. Thiosugars with sulfur outside the ring: Synthesis and medicinal activity

15.4. Naturally occurring thiosugars: Medicinal activity

15.5. Conclusions

Acknowledgments

References

Part Three: Medicinal chemistry

Chapter 16: Implementing green chemistry for synthesis of cholesterol-lowering statin drugs

16.1. Introduction

16.2. Green chemistry in drug synthesis

16.3. Cholesterol-lowering drugs

16.4. Statins

16.5. Lovastatin and simvastatin

16.5.1. Background

16.5.2. Common production methods

16.5.2.1. Lovastatin

16.5.2.2. Simvastatin

16.5.3. Adoption of green technology

16.5.3.1. Green process for simvastatin

16.5.3.2. Green process for lovastatin

16.6. Adoption of green chemistry for other statins

16.6.1. Green process for atorvastatin

16.6.2. Green process for rosuvastatin

16.6.3. Partial green process for pravastatin

16.7. Green chemistry in statin analysis

16.8. Future direction of green chemistry for statins

16.9. Summary

Acknowledgment

References

Chapter 17: Sustainable release of nanodrugs: A new biosafe approach

17.1. Introduction

17.2. Problems of conventional drug delivery

17.3. Why sustainable drug delivery is important?

17.4. Why nanomaterials are promising as nanodrug?

17.5. Different nanoparticles as nanodrug and advantages

17.5.1. Liposomal nanocarriers

17.5.2. Polymer-based NPs in drug delivery

17.5.3. Albumin NPs in drug delivery

17.5.4. Magnetic nanoparticles in drug delivery

17.5.5. Silicon dioxide in drug delivery

17.5.6. Zinc oxide in drug delivery

17.5.7. Selenium in drug delivery

17.5.8. Dendrimers in drug delivery

17.5.9. Carbon nanotube in drug delivery

17.5.10. Graphene oxide in drug delivery

17.6. Stimuli-responsive drug delivery by nanoparticles: A new dimension in drug delivery

17.6.1. pH-induced drug release

17.6.2. Temperature-induced drug delivery

17.6.3. Ultrasound-triggered drug delivery

17.7. Conclusion

References

Further reading

Chapter 18: Stimuli-responsive sugar-derived hydrogels: A modern approach in cancer biology

18.1. Introduction

18.2. Basic concepts of hydrogels

18.3. Classifications of hydrogels

18.3.1. Chemically cross-linked hydrogels

18.3.1.1. Small-molecule cross-linking

18.3.1.2. Photo-cross-linking

18.3.1.3. Polymer-polymer cross-linking or hybrid polymer networks

18.3.1.4. Interpenetrating networks

18.3.1.5. Enzymatic cross-linking

18.3.2. Physically cross-linked (reversible hydrogels)

18.3.2.1. Cross-linking via hydrophobic interaction

18.3.2.2. Cross-linking via ionic complexes

18.3.2.3. Cross-linking via polyelectrolyte complexes

18.4. Benefits of sugar-derived hydrogel for biological applications

18.5. Characteristic of stimuli-responsive sugar-derived hydrogels

18.5.1. Temperature-responsive hydrogels

18.5.2. pH-Responsive hydrogels

18.5.3. Light-responsive hydrogels

18.5.4. Electric current responsive hydrogels

18.5.5. Sound responsive hydrogels

18.5.6. Redox-responsive hydrogels

18.5.7. Solvent-responsive hydrogels

18.5.8. Glucose-responsive hydrogels

18.6. Hydrogels as in vitro cell culture models

18.7. Biomimetic hydrogels in the study of MCS

18.8. Hydrogels as engineered tissue microenvironment

18.9. Role of hydrogels as drug delivery systems in cancer cells

18.10. Recent advancements in anticancer drug delivery

18.11. Conclusion and future perspectives

References

Further reading

Chapter 19: Green synthesis and biological evaluation of anticancer drugs

19.1. Introduction

19.1.1. Types of cancer

19.1.2. Major features of cancer

19.1.3. Signs and symptoms

19.1.4. Etiology of cancer

19.1.5. Treatment of cancer

19.1.6. Chemistry, MOA, and uses anticancer drugs

19.1.7. Adverse effects and toxicities of anticancer drugs

19.1.8. Synthesis of commonly used anticancer drugs [22]

19.1.9. Conventional synthesis of anticancer drugs

19.1.10. Green synthesis for development of new anticancer agents

19.1.10.1. Quinoline derivatives as anticancer agents

19.1.10.2. Coumarin derivatives as anticancer agents

19.1.10.3. Synthesis of Imatinib as anticancer agents

19.1.10.4. Synthesis of thiadiazole derivatives as anticancer agent

19.1.10.5. Benzimidazole derivatives as anticancer agents

19.1.10.6. Pyrrole derivatives as anticancer agents

19.1.10.7. Ferulic acid amide derivatives as anticancer agents

19.1.10.8. Pyridine derivatives as anticancer agents

19.1.10.9. Thiazoles as anticancer agents

19.1.10.10. Quinazoline as anticancer agents

19.1.10.11. Pyrazole as anticancer agents

19.1.10.12. Indole derivatives as anticancer agents

19.1.10.13. Pinostrobin as anticancer agent

19.1.10.14. Pyrimidine derivatives as anticancer agents

19.1.10.15. Miscellaneous

19.2. Conclusion

Acknowledgment

References

Chapter 20: Green chemistry and synthetic approaches in the development of antidepressant and antips

20.1. Introduction

20.1.1. Selective serotonin reuptake inhibitors

20.1.2. Serotonin-norepinephrine reuptake inhibitors

20.1.3. Monoamine oxidase inhibitors

20.1.4. Tricyclic antidepressant

20.1.5. Norepinephrine-dopamine reuptake inhibitor

20.2. Conclusion

Acknowledgments

References

Part Four: Natural products

Chapter 21: Natural spices in medicinal chemistry: Properties and benefits

21.1. Introduction

21.2. General features of spices

21.3. General and chemical features of spices

21.4. Phytochemical composition

21.5. Pharmacological activities of ajwain

21.5.1. Antimicrobial activity

21.5.2. Antiinflammatory activity

21.5.3. Antifilarial activity

21.5.4. Antilithiasis and diuretic activities

21.5.5. Antitussive effects

21.5.6. Anthelmintic activity

21.5.7. Antihypertensive, antispasmodic, and broncho-dilating activities

21.5.8. Antiplatelet-aggregatory

21.5.9. Hepatoprotective activity

21.5.10. Ameliorative effect

21.5.11. Antiflatulant

21.5.12. Detoxification of aflatoxins

21.5.13. Hypolipidemic action in vivo

21.5.14. Nematicidal activity

21.6. Pharmacological activities of cumin

21.6.1. Antimicrobial activity

21.6.2. Antioxidant activity

21.6.3. Anticarcinogenic/antimutagenic

21.6.4. Antidiabetic activity

21.6.5. Immunomodulatory activity

21.6.6. Antiosteoporotic/estrogenic activity

21.6.7. Central nervous system

21.6.8. Bioavailability enhancer

21.7. Pharmacological activities of fennel

21.7.1. Antibacterial activity

21.7.2. Antifungal activity

21.7.3. Antioxidant activity

21.7.4. Antiinflammatory activity

21.7.5. Antianxiety activity

21.7.6. Gastro-protective activity

21.7.7. Estrogenic activity

21.7.8. Antidiabetic activity

21.7.9. Anticancer activity

21.8. Conclusions

Acknowledgments

References

Further reading

Chapter 22: Medicinal plants and their compounds with anticancer properties

22.1. Introduction: Background of medicinal plants

22.2. Value of medicinal plants

22.3. Medicinal plants with anticancer properties

22.3.1. Solanum nigrum

22.3.2. Cynodon dactylon

22.3.3. Tinospora cordifolia

22.3.4. Momordica dioica

22.3.5. Barleria grandiflora

22.3.6. Moringa oleifera

22.3.7. Cucurbita maxima

22.3.8. Terminalia chebula

22.4. Plant-derived anticancer agents in clinical use

22.5. Plant-derived anticancer drugs

22.5.1. Apoptosis

22.5.2. Enzyme inhibitor

22.6. Conclusions

Acknowledgments

References

Further reading

Part Five: Microwave-induced chemistry

Chapter 23: Microwave-assisted synthesis of antitubercular agents: A novel approach

23.1. Introduction

23.1.1. Tuberculosis

23.1.2. Microwave chemistry

23.1.3. Importance of MW in the synthesis of new anti-TB entities

23.1.3.1. Pyrimidine derivatives as antitubercular agents

23.1.3.2. Thiadiazole derivatives as antitubercular agents

23.1.3.3. Benzodiazepines derivatives as antitubercular agents

23.2. SAR study of 1,4-benzodiazepines derivatives

23.2.1. Hydantoins as antitubercular agents

23.2.2. Chalcones as antitubercular agents

23.2.3. Quinoline derivatives as antitubercular agents

23.2.4. Triazines as antitubercular agents

23.2.5. Phenothiazine analogs as antitubercular agents

23.2.6. Benzocoumarin-benzothiazepine hybrids as antitubercular agents

23.2.7. 1,3,4-Oxadiazoles as antitubercular agents

23.2.8. Benzothiazoles as antitubercular agents

23.2.9. Indole analogs as antitubercular agents

23.2.10. Piperazines as antitubercular agents

23.2.11. Pyrazolines as antitubercular agents

23.2.12. Benzimidazoles as antitubercular agents

23.3. Structure-activity relationship (SAR) study

23.3.1. Pyridine derivatives as antitubercular agents

23.3.2. Thiazolidine derivatives as antitubercular agents

23.3.3. 1,3-Oxazole derivatives as antitubercular agents

23.3.4. Pyrazinamide-Mannich bases as antitubercular agents

23.3.5. 1,2,3-Triazoles as antitubercular agents

23.4. Future perspective

23.5. Conclusion

Acknowledgments

References

Chapter 24: Microwave-induced synthesis of steroids and their chemical manipulations

24.1. Microwave background

24.2. Microwave in steroid synthesis

24.3. Microwave in the synthesis of compounds based on the properties (cholesterol, hormone, bile ac

24.4. Comparison of microwave vs classical method

24.5. Conclusion

Acknowledgments

References

Chapter 25: Microwave-induced synthesis as a part of green chemistry approach for novel antiinflamma

25.1. Inflammation

25.1.1. Acute inflammation

25.1.2. Chronic inflammation

25.1.3. Mediators of inflammation

25.2. Importance of antiinflammatory drugs

25.2.1. Nitric oxide (NO)-donating NSAIDs (NO-NSAIDs)

25.2.2. Selective COX-2 inhibitors

25.2.3. Dual COX/LOX inhibitors

25.2.4. Ipoprotein-PLA2 inhibitors

25.2.5. Microsomal prostaglandin E2 synthase inhibitors

25.2.6. TNF-α inhibitors

25.3. Introduction to microwave technique

25.3.1. Microwaves

25.3.2. Mechanism of microwave heating

25.3.3. Benefits of microwave-assisted synthesis

25.3.4. Microwave synthesis apparatus

25.3.4.1. Single-mode microwave apparatus

25.3.4.2. Multimode microwave apparatus

25.3.5. Applications of microwave-assisted synthesis

25.3.6. Microwave-assisted synthesis of novel antiinflammatory agents

Acknowledgments

References

Part Six: Computers in drug discovery

Chapter 26: Dipole moment in medicinal research: Green and sustainable approach

26.1. Background on dipole moment

26.1.1. 2-Pyrrolidone

26.1.2. Cholestanone

26.1.3. Purines, pyrimidines, and azines

26.1.4. Thiophene and carboxamides

26.2. Dipole moment and anticancer activity

26.2.1. Organometallic bismuth (III) compounds

26.2.2. Topovale

26.2.3. MDMA

26.2.4. Efavirenz (EFZ)

26.2.5. Adriamycin and daunomycin

26.2.6. Methotrexate, temozolomide, carmustine, tamoxifen, and hydroxifen

26.2.7. Ruthenium azopyridine complex

26.2.8. Glutamine

26.2.9. Lantadenes

26.2.10. Xanthone

26.2.11. Fullerene C60 and benzopyrene

26.2.12. Coumarins

26.3. Dipole moment and antifungal activity

26.3.1. Thiosemicarbazide

26.3.2. Pyrazolopyridines

26.3.3. Oxadiazoles

26.3.4. Beta-pinene (β-pinene)

26.3.5. Indol-4-one

26.3.6. Aminobenzenesulfonamide Schiff bases

26.3.7. Chalcones and chromanes

26.4. Dipole moment and antibacterial activity

26.4.1. Copper (II) complexes with quinolones and nitrogen-donor heterocycles

26.4.2. Thiourea derivatives

26.4.3. Indolylpyrimidines

26.4.4. Terpenes and phenylporpanes

26.4.5. Quinazolinone

26.4.6. Azole-derived compounds

26.4.7. Polyphenols

26.5. Dipole moment and various other medical disorders (antimicrobial, antimalarial, and antileishm

26.5.1. Hydrazide analogs

26.5.2. Phenothiazine (PTZ)

26.5.3. Thiazolidine

26.5.4. Cinchona alkaloids

26.5.5. Tetraoxanes

26.5.6. Chalcones

26.5.7. Cimetidine analogs

26.6. Conclusions

Acknowledgments

References

Chapter 27: Computational methods and tools for sustainable and green approaches in drug discovery

27.1. Introduction

27.2. QSAR, 3D QSAR, and ligand-based drug design

27.2.1. Why there is a need for QSAR?

27.2.2. Ligand-based virtual screening

27.3. Structure-based drug design and virtual screening strategy

27.3.1. Binding site detection, protein, and ligand refinement

27.3.2. Direct docking

27.3.3. Structure-based pharmacophore screening

27.3.4. Analysis of the hits

27.3.5. Similarity searching

27.3.6. Homology modeling

27.4. Drugability