Medicinal Chemistry of Anticancer Drugs

3rd Edition - April 28, 2023
Authors: Carmen Avendaño, J. Carlos Menéndez
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 8 5 4 9 - 0
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 9 6 5 2 - 6

This third edition of Medicinal Chemistry of Anticancer Drugs, provides an updated resource for students and researchers from the point of view of medicinal chemistry and drug desi… Read more

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This third edition of Medicinal Chemistry of Anticancer Drugs, provides an updated resource for students and researchers from the point of view of medicinal chemistry and drug design, focusing on the mechanism of action of antitumor drugs from the molecular level, and on the relationship between chemical structure and chemical and biochemical reactivity of antitumor agents.

Antitumor chemotherapy is a very active field of research, and a huge amount of information on the topic is generated every year. This new edition includes updated sections on the hot topic of cancer immunotherapy, cancer polypharmacology, multitargeted cancer therapy, medicinal chemistry of cancer diagnosis, theranostic anticancer agents, and pre-mRNA processing in cancer. Although many books are available that deal with clinical aspects of cancer chemotherapy, this book provides a unique and valuable perspective from the point of view of medicinal chemistry and drug design. It will be useful to undergraduate and postgraduate students of medicinal chemistry, pharmacology, biological chemistry, pharmacy and other health sciences. Researchers and practitioners will find a comprehensive treatment of the topic and a large number of references to reviews and the primary literature.

Cover
Title page
Table of Contents
Copyright
Preface
Abbreviations
Chapter 1: General aspects of cancer therapy
Abstract
1: Introduction: Some general comments about cancer and cancer therapy
2: Tumorigenesis and oncogenes. First advances in the knowledge of cancer
3: Early diagnosis of cancer and its therapeutic relevance
4: The problem of anticancer drug resistance
5: Medicinal chemistry and the evolution of cancer chemotherapy
6: A brief comment of cancer nanotechnology
7: Cancer immunotherapy
8: The shift from single-drug targeted therapy to combinatorial and personalized therapies in cancer
9: A summary of FDA-approved anticancer drugs
References
Chapter 2: Antimetabolites
Abstract
1: Introduction
2: Inhibitors of the biosynthesis of uridylic acid
3: Inhibitors of ribonucleotide reductase
4: Inhibitors of the biosynthesis of thymidylic acid
5: Inhibitors of dihydrofolate reductase (DHFR)
6: Inhibitors of the de novo purine biosynthesis pathway
7: Inhibitors of adenosine deaminase
8: Inhibitors of late stages in DNA synthesis
9: Antimetabolite enzymes
References
Chapter 3: Anticancer drugs that modulate hormone action
Abstract
1: Introduction
2: Estrogens and their involvement in carcinogenesis
3: Antiestrogens as antitumor drugs
4: Aromatase inhibitors
5: Steroid sulfatase inhibitors
6: Androgen-related antitumor agents
7: Regulation of gonadotropin-releasing hormone (GnRH, LHRH). Control of the hypothalamic-pituitary-gonadal axis
8: Miscellaneous steroid hormone-related anticancer therapy
9: Compounds acting on other proteins of the nuclear receptor superfamily
10: Indirect inhibitors of the activation of nuclear receptors
11: PPAR ligands as antitumor agents
12: Somatostatin analogs for the treatment of neuroendocrine tumors
References
Chapter 4: Anticancer strategies involving radical species
Abstract
1: Introduction: Radicals and other reactive oxygen species
2: Biological effects of reactive oxygen species
3: Anthracyclines and their analogs
4: Mitoxantrone and related quinones
5: Actinomycin D
6: Elsamicin A, chartreusin and related compounds
7: Bleomycins
8: Enediyne antibiotics
9: Tirapazamine
10: Penclomedine
11: Radiotherapy and radiosensitizers
12: Photosensitizing agents. Photodynamic therapy of cancer
References
Chapter 5: DNA alkylating agents
Abstract
1: Introduction
2: Nitrogen mustards
3: Aziridines (ethyleneimines)
4: Epoxides and their precursors
5: Methanesulfonates
6: Nitrosoureas
7: Triazenes
8: Methylhydrazines
9: 1,3,5-Triazines: Hexamethylmelamine and trimelamol
10: Transition metal species
11: Miscellaneous alkylating and acylating antitumor agents
References
Chapter 6: Anticancer drugs that interact with the DNA minor groove
Abstract
1: Introduction
2: Netropsin, distamycin and related compounds
3: Mitomycins
4: Tetrahydroisoquinoline alkaloids
5: Cyclopropylindole alkylating agents
6: Irofulven
7: Pyrrolo[1,4]benzodiazepines
References
Chapter 7: DNA intercalation and topoisomerase inhibition
Abstract
1: DNA intercalation and its consequences
2: Monofunctional intercalating agents
3: Bifunctional intercalating agents
4: Indirect DNA damage by DNA topoisomerase inhibitors
5: Specific topoisomerase I inhibitors
6: Specific topoisomerase II poisons and inhibitors
7: Dual topoisomerase II inhibitors
8: Telomerase inhibitors and other anticancer approaches targeting telomers
9: DNA repair inhibitors
References
Chapter 8: Epigenetic therapy of cancer
Abstract
1: Introduction
2: DNA methylation as an epigenetic target
3: Modulation of chromatin-related epigenetic processes
4: Other aspects of the epigenetic therapy of cancer
References
Chapter 9: Anticancer drugs targeting tubulin and microtubules
Abstract
1: Introduction
2: Drugs that inhibit microtubule polymerization
3: Microtubule-stabilizing agents: Compounds binding at the taxane site
4: Miscellaneous anticancer drugs acting on tubulin sites
5: Antivascular effects of microtubule-targeted agents: Vascular disrupting agents
6: Epigenetic control of tubulin function
7: Compounds acting at microtubular targets different from tubulin
References
Chapter 10: Anticancer drugs acting on signaling pathways, part 1: Tyrosine kinase inhibitors
Abstract
1: Introduction
2: The role of protein kinases in cancer
3: Inhibitors of tyrosine kinases: General aspects
4: Inhibitors of epidermal growth factor receptors
5: Inhibitors of insulin-like growth factor receptors (IGF-1R)
6: Inhibitors of hepatocyte growth factor receptor (HGFR, c-Met)
7: Inhibitors of pro-angiogenic tyrosine kinases: VEGFR and related receptors
8: Inhibitors of FLT3 (CD135)
9: Inhibitors of BCR-ABL tyrosine kinase (Abelson kinase)
10: Anaplastic lymphoma kinase (ALK) inhibitors
11: Inhibitors of the JAK-STAT and PRL pathways
12: Inhibitors of Bruton’s tyrosine kinase (BTK)
13: Inhibitors of tropomyosin receptor kinase (TRK)
14: Inhibitors of spleen tyrosine kinase (SYK)
References
Chapter 11: Anticancer drugs acting on signaling pathways, part 2: Inhibitors of serine-threonine kinases and miscellaneous signaling pathways
Abstract
1: Inhibitors of serine-threonine kinases
2: Inhibitors of the Ras/Raf/MEK signaling pathways
3: Transforming growth factor-β (TGF-β)-Smad signaling
4: Kinases involved in glycolysis
References
Chapter 12: Protein degradation-based cancer therapy
Abstract
1: Introduction
2: Proteolytic enzymes as anticancer targets
3: Targeted protein degradation as a therapeutic strategy in cancer
References
Chapter 13: Cancer immunotherapy
Abstract
1: Cancer immunotherapy: A brief history
2: Cancer immunotherapy: General aspects
3: Antibodies as immune checkpoint inhibitors
4: Antibodies as immunomodulators
5: Miscellaneous antibodies for immunotherapy
6: Cytokines and chemokines
7: Adoptive cell therapies
8: Small-molecule immunotherapy of cancer
9: Bacteria and bacterial toxins for cancer therapy
10: Cancer vaccines
11: Immunomodulatory gene therapy
References
Chapter 14: Miscellaneous small- molecule and biological approaches to targeted cancer therapy
Abstract
1: Antiangiogenic compounds acting on nonkinase targets
2: Therapies targeting cancer stem cells
3: Antagonists of chemokine receptors
4: Anticancer drugs targeting apoptotic signaling pathways
5: Anticancer drugs targeting autophagy
6: Inhibitors of heat-shock proteins (Hsps) and other chaperones
7: Thioredoxin as a target in cancer therapy
8: Inhibitors of hypoxia-inducible factors (HIFs)
9: Miscellaneous biological approaches to cancer therapy
References
Chapter 15: Drug targeting in anticancer chemotherapy
Abstract
1: Introduction
2: Prodrug-based anticancer drug targeting
3: Polymer conjugates. Macromolecular small-drug carrier systems
4: Antibody-drug conjugates
5: Polymer-directed enzyme prodrug therapy approaches
6: Folate receptor-targeted chemotherapy
7: Nanoparticles in anticancer drug targeting
References
Chapter 16: Drugs that modulate resistance to antitumor agents
Abstract
1: Introduction
2: ABC efflux pumps in anticancer drug resistance
3: Glutathione and glutathione-S-transferase in anticancer drug resistance
4: Chemosensitizers targeting DNA-repair systems
5: Antitumor drug resistance related to tumor microenvironment. Extracellular pH
6: The role of the SPARC protein in drug resistance
7: Antitumor drug resistance related to cellular adhesion molecules
8: Other tumor chemoresistance mechanisms
9: Radioresistance and tumor radiosensitization
References
Chapter 17: Cancer chemoprevention
Abstract
1: Introduction
2: Cancer biomarkers, molecular medicine, and individualized treatments
3: Cancer chemoprevention: General aspects
4: Chemopreventive agents
5: Dietary components and phytochemicals in cancer chemoprevention
6: Compounds with miscellaneous protective mechanisms
7: Targeting nutrient metabolism with approved drugs and its role in cancer chemoprevention
References
Index

Carmen Avendaño

Mª del Carmen Avendaño López received her doctoral degree in Pharmacy at the Complutense University of Madrid (UCM) in 1970. In 1986, she became Full Professor of Organic Chemistry at the Department of Organic and Pharmaceutical Chemistry of this university, being responsible for one of its research groups. Between 1993 and 2009, she was a member of the Scientific Advising Committee for the Profarma Program, organized by the Spanish Ministry for Industry to incentivize research activities at the pharmaceutical industry. She was appointed Vice-rector in charge of Postgraduate Degrees at the International University “Menéndez y Pelayo” in 2005-2007. She participated in the development of the Spanish Society for Therapeutical Chemistry and has also been a member of several scientific international societies and assessment committees. Since 1999, she is a Fellow of the Spanish National Royal Academy of Pharmacy where she is in charge of all activities related to Medicinal Chemistry, with particular focus on the relevance of chemistry in drug discovery and development. She has co-authored several chapters in periodical series and encyclopedias, including “Comprehensive Heterocyclic Chemistry” and “Science of Synthesis”, and has edited and co-authored several Medicinal Chemistry textbooks, most notably “Introducción a la Química Farmacéutica”, published by McGraw-Hill Interamericana in 1993 and 2001. In 2008, she co-authored with Dr. Menéndez the first edition of “Medicinal Chemistry of Anticancer Drugs“ for Elsevier. Her research activities, documented in about 200 publications and some patents in collaboration with the pharmaceutical industry, have dealt with the development of synthetic methodologies to obtain biologically active molecules, with particular focus on antitumor natural compounds.

Affiliations and expertise

Organic and Medicinal Chemistry Unit, Faculty of Pharmacy, Complutense University, Madrid, Spain

J. Carlos Menéndez

José Carlos Menéndez was born in Madrid (1960) and obtained degrees in Pharmacy from Universidad Complutense at Madrid, UCM (1982, with Excellence Award) and Chemistry from UNED (1985) followed by a Ph.D. in Pharmacy from UCM in 1988, under the supervision of Dr. Mónica M. Söllhuber, with Excellence Award. In August 1988, he joined the group of Professor Steven V. Ley at Imperial College, London, where he worked on the total synthesis of the natural ionophoric antibiotic routiennocin. In September 1989, he returned as a Profesor Titular to the Organic and Medicinal Chemistry Department at UCM, where he has pursued his teaching and research career ever since, having obtained Accreditation as a Full Professor in 2010. He has varied research interests, related, on one hand, to medicinal chemistry work in the fields of neurodegeneration (prion disease, Alzheimer’s disease, ischemic injury) and chemotherapy (cancer, tuberculosis, leishmaniasis). Other projects pursued in his group are focused on the development of new synthetic methodology, including work on microwave-assisted organic synthesis, CAN as a catalyst for organic synthesis, green chemistry and the development new domino and multicomponent reactions for the preparation of biologically relevant bicyclic systems and nitrogen heterocycles. This work has been documented in about 210 research papers, reviews and chapters and 9 patents. Additionally, he has co-authored two textbooks in Medicinal Chemistry for McGraw-Hill Interamericana (?Introducción a la Química Farmacéutica, 2nd Ed." 2001 and "Ejercicios de Química Farmacéutica", 1997), and a third one for Elsevier ("Medicinal Chemistry of Anticancer Drugs", 2008). He is the coordinator of a Master Course on Drug Discovery, and the coordinator at UCM of a Ph.D. program in Medicinal Chemistry. He has collaborated with many research groups in UK, Italy, France, and India and also has some long-standing collaborations with several chemical and pharmaceutical Spanish companies. He has been the head of the Organic Microanalysis service at UCM since its creation in 1991. Since 2004, he is a Corresponding Member of the Spanish Royal Academy of Pharmacy. He has been a Visiting Professor at Université Paul Cézanne (Aix-Marseille III, France) in 2007 and at the Istituto di Studi Avanzati (ISA), Bologna University, Italy, in 2014.