Advances in Prodrugs
Design and Therapeutic Applications
- 1st Edition - September 25, 2024
- Imprint: Elsevier
- Editors: Claudiu Trandafir Supuran, Andrea Angeli, Damiano Tanini
- Language: English
- Paperback ISBN:9 7 8 - 0 - 4 4 3 - 1 5 6 3 5 - 9
- eBook ISBN:9 7 8 - 0 - 4 4 3 - 1 5 6 3 4 - 2
Advances in Prodrugs: Design and Therapeutic Applications provides a versatile tool in prodrug design and development as well as a concrete perspective on clinical and preclinical… Read more
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Request a sales quoteAdvances in Prodrugs: Design and Therapeutic Applications provides a versatile tool in prodrug design and development as well as a concrete perspective on clinical and preclinical studies currently available on prodrugs. The first part of this book discusses different chemical classes of prodrugs, with particular emphasis on metabolic pathways and mechanisms involved in the activation of their functional groups. The second part of the book covers therapeutic applications of prodrugs against the most discussed diseases, providing detailed discussion on recent achievements in the field. This book offers researchers involved in drug discovery key criteria for the successful development of prodrug-based therapeutic tools.
Prodrugs are inactive drug precursors which undergo different chemical transformation by metabolic processes to provide pharmacologically active compounds. Prodrugs include a broad range of structurally diverse molecules employed for the treatment of several diseases.
Prodrugs are inactive drug precursors which undergo different chemical transformation by metabolic processes to provide pharmacologically active compounds. Prodrugs include a broad range of structurally diverse molecules employed for the treatment of several diseases.
- Highlights chemistry and pharmacology-related aspects, offering a versatile tool for readers involved in prodrug development and study
- Discusses in-depth treatment of several activation mechanisms and applications for disease treatments
- Covers a range of topics from basic contents, design, and mechanisms of actions to current applications in drugs
Postgraduate students and researchers working with drug discovery, medicinal chemistry, pharmacology, bioorganic and bioinorganic chemistry
- Advances in Prodrugs
- Cover image
- Title page
- Table of Contents
- Copyright
- Contributors
- Editors biography
- Part I: Introduction
- Chapter 1 Prodrugs: General concepts and prodrug design in medicinal chemistry
- Abstract
- Keywords
- 1 Drug development and concept of prodrug
- 2 Prodrugs: Classification criteria
- 3 Why are prodrugs developed? (Drugs vs prodrugs: A critical comparison)
- 4 Pharmacokinetics and pharmacodynamics of prodrugs
- 5 State of the art of prodrug research
- References
- Part II: Activation mechanisms and related functional groups
- Chapter 2 pH-sensitive prodrugs
- Abstract
- Keywords
- 1 Introduction
- 1.1 Prodrugs: General definition and brief overview of pH-sensitive prodrugs
- 2 pH differences at cellular levels
- 3 pH-responsive functional groups
- 4 Benefits of pH-sensitive prodrugs
- 4.1 Targeting physiological conditions for site-selective delivery and/or activation
- 4.2 Prolonged duration of action and improved metabolic stability
- 5 Conclusions
- References
- Chapter 3 Enzyme-mediated activation of prodrugs
- Abstract
- Keywords
- 1 Introduction
- 2 Enzyme classes
- 2.1 Oxidoreductases
- 2.2 Transferases
- 2.3 Hydrolases
- 2.4 Lyases
- 2.5 Isomerases
- 2.6 Ligases and translocases
- References
- Chapter 4 Reactive oxygen species-responsive prodrugs
- Abstract
- Keywords
- 1 Introduction
- 2 Physiological roles of ROS and oxidative stress-related diseases
- 2.1 Physiological role of reactive oxygen species
- 2.2 Pathological role of ROS
- 3 ROS-responsive prodrugs: Activation mechanisms
- 4 ROS-responsive functional groups for prodrug design
- 5 Therapeutic applications of ROS-responsive prodrugs
- 5.1 Therapeutic applications in cancer
- 5.2 Therapeutic application in inflammation
- 6 Conclusion
- References
- Chapter 5 Photoactivatable prodrugs
- Abstract
- Keywords
- 1 Introduction
- 2 Nitroaryl-based photocleavable protecting groups
- 3 Coumarin-based photocleavable protecting groups
- 4 BODIPY-based photocleavable protecting groups
- 5 Carbonyl-based photocleavable protecting groups
- 6 Metal complex-based photocleavable protecting groups
- 7 Heptamethine dye-based NIR photocleavable protecting groups and other PPGs
- 8 Gasotransmitter prodrugs
- 9 Conclusions
- References
- Chapter 6 Antibody-directed enzyme prodrug therapy (ADEPT)
- Abstract
- Keywords
- 1 Introduction
- 2 The antibody
- 3 The enzyme/prodrug system
- 3.1 D-amino acid oxidase
- 3.2 Carboxypeptidase G2
- 3.3 β-Glucuronidase
- 3.4 β-Lactamase
- 4 Clinical studies
- 4.1 A5B7-F(ab)2-CPG2 + SB43gal + CMDA prodrug
- 4.2 A5B7-F(ab)2-CPG2 + SB43gal + CMDA prodrug
- 4.3 A5B7-F(ab)2-CPG2 + BIP prodrug
- 4.4 MFECP1 fusion protein + BIP prodrug (single cycle)
- 4.5 MFECP1 fusion protein + BIP prodrug (repeated cycle)
- 5 Immunogenicity
- 6 Conclusions
- References
- Chapter 7 Self-assembling prodrugs
- Abstract
- Keywords
- 1 Introduction
- 2 A brief taxonomy of prodrugs, with an emphasis on the advanced ones
- 3 Supramolecular prodrugs
- 3.1 Prodrugs of the class of cavity-size-dependent host-guest complexes
- 3.2 Prodrugs of the class of dynamic assemblies
- 3.3 Prodrugs of the class of (self-)structured nanoentities
- 4 Final considerations
- 4.1 The issue of the reproducibility of prodrugs functionality
- 4.2 The vision of prodrug strategy related to supramolecular prodrugs
- References
- Chapter 8 Prodrug-based nanomedicines: A successful rationale to design novel and effective delivery strategies
- Abstract
- Keywords
- 1 Introduction
- 2 Nanocarriers as efficient drug delivery systems
- 2.1 Polymeric nanocarriers
- 2.2 Lipid nanocarriers
- 2.3 Some paradigmatic examples
- 3 Conclusions and future perspectives
- References
- Chapter 9 Hypoxia-activated prodrugs
- Abstract
- Keywords
- 1 Tumor hypoxia
- 1.1 HIF-1α, the master regulator of tumor hypoxia
- 1.2 HIF-1α induction of P-glycoprotein
- 1.3 HIF-1α roles in WE and RWE
- 1.4 HIF-1α induction of CA IX
- 1.5 HIF-1α induction of angiogenesis
- 1.6 HIF-1α induction of epithelial-mesenchymal transition
- 1.7 HIF-1α induction of glutathione
- 2 Targeting tumor hypoxia
- 2.1 Enhancing tumor oxygenation
- 2.2 Antiangiogenesis agents
- 2.3 Targeting HIF-1α
- 2.4 Impeding HIF targets incorporated in the modulation of TME acidity
- 2.5 Inhibiting HIF targets involved in the EMT
- 2.6 Targeting mitochondrion dysfunction
- 2.7 Targeting stromal-epithelial metabolic coupling (RWE)
- 2.8 Generating ROS strategy
- 3 Hypoxia-activated prodrugs (HAPs)
- 3.1 Mechanism of HAPs activation
- 4 Classes of hypoxia-activated prodrugs
- 4.1 Nitro-based prodrugs
- 4.2 Quinone prodrugs
- 4.3 Aromatic N-oxides
- 4.4 Aliphatic N-oxides
- 5 HAPs as theranostic agents
- 6 Hypoxia-activated PROTACs
- References
- Part III: Application of prodrugs in the treatment of diseases
- Chapter 10 Antiviral and antiretroviral prodrugs
- Abstract
- Keywords
- 1 Introduction
- 2 Nucleosides and their derivatives
- 3 Acyclic nucleosides and phosphonates
- 4 Nonnucleoside reverse transcriptase inhibitors (NNRTs)
- 5 Protease inhibitors
- 6 Viral entry and attachment inhibitors
- 7 Miscellaneous drugs in clinical trials
- 8 Conclusions
- References
- Chapter 11 Prodrugs for cancer therapy
- Abstract
- Keywords
- 1 Introduction
- 2 Metal-based prodrugs in cancer therapy
- 2.1 Platinum-based chemotherapeutics
- 2.2 Ruthenium-based chemotherapeutics
- 3 Natural and semisynthetic prodrugs in cancer therapy
- 3.1 Taxane prodrugs
- 3.2 Camptothecin prodrugs
- 3.3 Combretastatin prodrugs
- 3.4 Coumarin as prodrugs in cancer therapy
- 4 Antibody-drug conjugates
- 5 Clinical prodrugs of established anticancer agents in oncology
- 6 Conclusion
- References
- Chapter 12 Prodrugs for neurodegenerative diseases
- Abstract
- Keywords
- 1 Introduction
- 2 Alzheimer’s disease
- 3 Treatment of Alzheimer’s disease
- 4 Prodrugs for AD
- 4.1 Prodrugs of galantamine, rivastigmine, and donepezil
- 4.2 Prodrugs of rivastigmine and donepezil
- 4.3 Prodrugs of memantine
- 5 Parkinson’s disease
- 6 Treatment of Parkinson’s disease
- 7 Prodrugs for PD
- 7.1 Prodrugs of dopamine and l-DOPA
- 7.2 Prodrugs of the other PD drugs
- 8 Conclusion
- References
- Chapter 13 Prodrugs in cardiovascular therapy
- Abstract
- Keywords
- General aspects
- 1 Prodrugs for vascular thrombosis
- 1.1 Antithrombin prodrugs
- 1.2 Antiplatelet prodrugs
- 2 Prodrugs for hypertension and pulmonary hypertension
- 2.1 Prodrugs for hypertension
- 2.2 Prodrugs for pulmonary hypertension
- 3 Prodrugs for atherosclerosis
- References
- Chapter 14 Prodrugs for ocular diseases
- Abstract
- Keywords
- 1 Introduction
- 2 Adrenergic agonist prodrugs
- 3 β-Adrenergic antagonist prodrugs
- 4 Prostaglandin-based prodrugs
- 5 Cholinergic prodrugs
- 6 Carbonic anhydrase inhibitor prodrugs
- 7 Steroid-based prodrugs
- 8 Antiviral prodrugs
- 9 Conclusions
- References
- Chapter 15 Antibacterial prodrugs
- Abstract
- Keywords
- 1 Introduction: Antibiotics and bacterial resistance
- 2 Prodrug applications against resistant bacterial pathogens
- 3 Using prodrugs to overcome bacterial resistance?
- 4 β-Lactamase-activated prodrugs
- 5 Cephalosporin-3′-diazeniumdiolates as prodrugs
- 6 Glycoside-based prodrugs
- 7 Pyrimidine nucleoside derivatives as prodrugs
- 8 Carvacrol prodrugs
- 9 Antimicrobial peptides-based prodrugs
- 10 Clinical and preclinical advances
- References
- Chapter 16 Prodrugs on neglected tropical diseases and therapeutic advances
- Abstract
- Keywords
- 1 Neglected tropical diseases
- 2 New drugs and therapeutic problems
- 3 Prodrugs
- 4 Prodrugs against trypanosomiasis
- 4.1 Chagas disease
- 4.2 Nitro heterocyclic prodrugs
- 4.3 Ester prodrugs
- 4.4 Benzoxaborole prodrug
- 4.5 Nitrofurazone and hydroxymethylnitrofurazone prodrugs
- 4.6 Fosravuconazole E1224 prodrug
- 5 Prodrugs against human African trypanosomiasis or sleeping sickness
- 5.1 Fexinidazole prodrug
- 5.2 Melarsoprol prodrug
- 5.3 Pafuramidine (DB289) prodrug
- 5.4 N,N-Dihydroxypentamidine and N,N-bis(succinyloxy) pentamidine prodrugs
- 6 Prodrugs against leishmaniasis
- 7 Prodrugs against schistosomiasis
- 7.1 Oxamniquine
- 7.2 New prodrugs
- 8 Antimalarial prodrugs
- References
- Index
- Edition: 1
- Published: September 25, 2024
- Imprint: Elsevier
- No. of pages: 380
- Language: English
- Paperback ISBN: 9780443156359
- eBook ISBN: 9780443156342
CT
Claudiu Trandafir Supuran
Claudiu T. Supuran received his BSc and PhD in Chemistry from the Polytechnic Univesity of Bucharest (Romania), where he became an Assistant and then Associate Professor of Chemistry. In 1995, he moved to University of Florence, where he is Full Professor. His main research interest focused in medicinal chemistry, design of enzyme modulators especially in the carbonic anhydrase field, X-ray crystallography and molecular biology of metalloenzymes. He has published more than 1900 papers in these fields and his Hirsch index is 155, with > 105 700 citations. One of the compounds discovered in his laboratory (SLC-0111) is in Phase II clinical trials for the treatment of advanced metastatic solid tumors in Canada/USA, whereas a monoclonal antibody of which he is co-discoverer (6A10) is in preclinical evaluation and anti-tumor theragnotic agent. He is the editor-in-Chief of Journal of Enzyme Inhibition and Medicinal Chemistry and of Expert Opinion on Therapeutic Patents.
Affiliations and expertise
University of Florence, NEUROFARBA Department (Italy)AA
Andrea Angeli
Andrea Angeli obtained his MSc in Medicinal Chemistry and Technologies in 2014 and his PhD in Medicinal Chemistry in 2019 at the University of Florence (Italy). After he spent three years as Assistant researcher at the Centre of Advanced Research in Bionano conjugates and Biopolymers Department, “Petru Poni” Institute of Macromolecular Chemistry (Romania). From 2020 is visiting researcher to University of Florence. His research deals with several aspects of metalloenzymes, spanning from drug design, X-ray crystallography and synthesis of enzyme modulators.
Affiliations and expertise
University of Florence, NEUROFARBA Department ItalyDT
Damiano Tanini
Damiano Tanini received his PhD degree in Chemistry in 2015 from the University of Florence working on the stereoselective synthesis of sulfur- and selenium-containing compounds. He carried out part of his doctoral research at the University of Bristol, working with Prof. V. K. Aggarwal. D. Tanini is currently a researcher in Organic Chemistry at the University of Florence. His research interests currently centre on organic synthesis, ranging from the development of sustainable methodologies towards bioactive molecules to the study of chalcogen-catalysed transformations and molecular chirality. D. Tanini serves as Editorial Board Member of several journals in chemical and biochemical area.
Affiliations and expertise
University of Florence, Department of Chemistry (Italy)Read Advances in Prodrugs on ScienceDirect