Advances in Prodrugs

Design and Therapeutic Applications

1st Edition - September 1, 2024
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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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 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.

PART 1 INTRODUCTION

1: PRODRUGS: GENERAL CONCEPTS, PRODRUG DESIGN IN MEDICINAL CHEMISTRY
- Drug development and concept of prodrug
- Prodrugs classification criteria
- Why are prodrugs developed? (Drugs vs prodrugs: A critical comparison )
- Pharmacokinetics and pharmacodynamics of prodrugs
- State-of-the art of prodrug research

PART 2 ACTIVATION MECHANISMS AND RELATED FUNCTIONAL GROUPS

2: pH-SENSITIVE PRODRUGS
- Introduction: definition and use of pH-sensitive prodrugs
- pH differences at cellular levels
- pH-responsive functional groups

3: ENZYME-MEDIATED ACTIVATION OF PRODRUGS
- Introduction
- Hydrolases-mediated activation of prodrugs
- Functional groups activated by hydrolytic enzymes
- Activation of prodrugs by oxidoreductases
- Functional groups activated by oxidoreductases
- Activation of prodrugs by transferases
- Functional groups activated by transferases
- Activation of prodrugs by lyases
- Functional groups activated by lyases
- Activation of prodrugs by isomerases
- Functional groups activated by isomerases

4: REACTIVE OXYGEN SPECIES-RESPONSIVE PRODRUGS
- Introduction
- Physiological roles of ROS and oxidative stress-related diseases
- ROS-responsive prodrugs: Activation mechanisms
- ROS-responsive functional groups for prodrug design
- Therapeutic applications of ROS-responsive prodrugs

5: PHOTOACTIVABLE PRODRUGS
- Introduction
- Photoresponsive systems and their therapeutic application
- Photoresponsive activation: functional groups and activation mechanisms

6: ANTIBODY DIRECTED ENZYME PRODRUG THERAPY (ADEPT)
- Introduction and definitions
- Functional groups and mechanisms involved in ADEPT
- Therapeutic applications

7: SELF-ASSEMBLING PRODRUGS
- Introduction and definitions
- Mechanisms in self-assembling prodrugs
- Conjugation and drug releasing
- Therapeutic applications

8: CARRIER-LINKED PRODRUGS
- Introduction and definitions
- Prodrug carriers
- Criteria for design and development

9: HYPOXIA-ACTIVATED PRODRUGS
- Hypoxia
- Promising targets for hypoxic tumour treatment
- Classes of hypoxia-activated prodrugs (quinones, nitroaromatics, aliphatic N-oxides and hetero- aromatic N-oxides)

PART 3 APPLICATION OF PRODRUGS IN THE TREATMENT OF DISEASES

10: ANTIVIRAL AND ANTIRETROVIRAL PRODRUGS
- Introduction and classification of antiviral prodrugs
- Prodrugs for the treatment of hepatitis B and C
- Prodrugs against HIV
- Prodrugs against cytomegalovirus
- Prodrugs against herpes simplex virus
- Prodrugs against coronaviruses (SARS, MERS)

11: PRODRUGS FOR CANCER THERAPY
- Promising prodrug targets for tumour treatment
- Clinical and preclinical developments in prodrug-based tumor treatment
-- Hypoxia-activated prodrugs: clinical and preclinical progresses
-- Antibody directed enzyme prodrug therapy (ADEPT) in cancer therapy – a critical discussion
- Choice of the prodrug to conjugate with the antibody
- ADEPT in cancer therapy: clinical and preclinical progresses

12: PRODRUGS FOR NEURODEGENERATIVE DISEASES
- General aspects
- Prodrugs for Alzheimer’s Disease
- Prodrugs for Parkinson’s Disease

13: PRODRUGS IN CARDIOVASCULAR THERAPY
- General aspects
- Prodrugs for vascular thrombosis
- Prodrugs for atherosclerosis
- Prodrugs for hypertension and pulmonary hypertension

14: PRODRUGS FOR INFLAMMATORY DISEASES
- Prodrugs for acute and chronic inflammation
- Prodrugs of Non-steroidal Anti-inflammatory Drugs
- Prodrugs for the treatment of inflammatory bowel diseases therapy
- Prodrugs for the treatment of chronic inflammatory pain
- Prodrugs for the treatment of rheumatoid arthritis
- Prodrugs for the treatment of other inflammation-related diseases

15: PRODRUGS FOR OCULAR DISEASES
- Introduction: ocular diseases and ocular drug delivery
- Adrenergic agonist prodrugs
- Beta adrenergic antagonist prodrugs
- Prostaglandin-based prodrugs
- Cholinergic prodrugs
- Carbonic anhydrase inhibitors (CAIs) prodrugs
- Steroid-based prodrugs

16: ANTIBACTERIAL PRODRUGS
- Introduction: antibiotics and bacterial resistance
- Using prodrugs to overcome bacterial resistance?
- β-Lactamase-activated prodrugs
- Cephalosporin-3’ –diazeniumdiolates as prodrugs
- Glycoside-based prodrugs
- Antimicrobial peptides-based prodrugs
- Pyrimidine nucleoside derivatives as prodrugs
- Carvacol prodrugs
- Clinical and preclinical advances

17: PRODRUGS AGAINST NEGLECTED DISEASES
- Neglected diseases and therapeutic advances
- Prodrugs against schistosomiasis
- Prodrugs against leishmaniosis
- Prodrugs against trypanosomiasis
- Antimalarial prodrugs

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)

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 Italy

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)