Medicinal chemistry of anticancer drugs /

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 che...

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Bibliographic Details
Main Author:	Avendaño, Carmen
Corporate Author:	ScienceDirect (Online service)
Other Authors:	Menéndez, J. Carlos
Format:	eBook
Language:	English
Published:	Amsterdam, Netherlands ; Oxford, United Kingdom ; Cambridge MA : Elsevier, [2023]
Edition:	Third edition.
Subjects:	Cancer > Chemotherapy. Drugs > Design. Pharmaceutical chemistry. Drug Design Chemistry, Pharmaceutical Cancer > Chimiothérapie. Médicaments > Conception. Chimie pharmaceutique. Cancer > Chemotherapy Drugs > Design Pharmaceutical chemistry Càncer. Quimioteràpia. Disseny de medicaments. Química farmacèutica. Electronic books. Llibres electrònics.
Online Access:	Connect to the full text of this electronic book

Table of Contents:

Intro
Medicinal Chemistry of Anticancer Drugs
Copyright
Contents
Preface
Abbreviations
Chapter 1 General aspects of cancer therapy
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
5.1 Natural products in cancer chemotherapy
5.2 Evolution of small-molecule-based cancer therapy
5.3 Protein-protein interactions as a target in anticancer drug discovery
5.4 Antibodies in cancer therapy
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
1 Introduction
2 Inhibitors of the biosynthesis of uridylic acid
3 Inhibitors of ribonucleotide reductase
3.1 Structure and catalytic cycle of ribonucleotide reductase
3.2 Gallium salts and complexes as RNR inhibitors
3.3 Radical scavengers as RNR inhibitors
3.4 Substrate analogs as RNR inhibitors
3.5 Allosteric inhibition of RNR via inhibition of purine nucleoside phosphorylase
4 Inhibitors of the biosynthesis of thymidylic acid
4.1 General comments on thymidylate synthase
4.2 5-Fluorouracil and floxuridine
4.3 5-Fluorouracil prodrugs
4.4 Modulation of 5-fluorouracil activity
4.4.1 Decreased degradation of 5-FU
4.4.2 Enhancement of the inhibition of thymidylate synthase by 5-FU
4.4.3 Enhancement of 5-FU activation
4.5 Uridine triacetate (vistonuridine), a 5-FU antidote
4.6 Trifluridine
4.7 Folate-based thymidylate synthase inhibitors.
7 Regulation of gonadotropin-releasing hormone (GnRH, LHRH). Control of the hypothalamic-pituitary-gonadal axis
7.1 Introduction
7.2 GnRH (LHRH) agonists
7.3 GnRH (LHRH) antagonists
8 Miscellaneous steroid hormone-related anticancer therapy
8.1 Gestagens as antitumor agents
8.2 Glucocorticoid modulators as antitumor agents
9 Compounds acting on other proteins of the nuclear receptor superfamily
9.1 Retinoids
9.2 Thyroid hormones
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
1 Introduction: Radicals and other reactive oxygen species
2 Biological effects of reactive oxygen species
2.1 Membrane phospholipid peroxidation
2.2 Malondialdehyde generation and its consequences
2.3 DNA strand cleavage
2.4 Oxidation of DNA bases
2.5 Oxidative stress induction as a strategy in cancer treatment
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
11.1 Radiotherapy
11.1.1 External beam radiotherapy (EBRT)
11.1.2 Brachytherapy (internal radiation therapy)
11.1.3 Radioisotope therapy (RIT)
11.1.4 Neutron irradiation
11.1.5 Proton therapy
11.1.6 Simultaneous imaging and radiotherapy: Theranostic radioisotopes
11.2 Drugs used as coadjuvants to radiotherapy
11.2.1 Radiosensitizers
11.2.2 Oxygen enhancement for radiosensitization
11.2.3 Radioprotectors in radiotherapy
12 Photosensitizing agents. Photodynamic therapy of cancer
12.1 General aspects of photodynamic therapy.
12.2 Porphyrins as photosensitizers
12.3 Nonporphirin photosensitizers
12.4 Other applications of photodynamic therapy
References
Chapter 5 DNA alkylating agents
1 Introduction
2 Nitrogen mustards
2.1 Introduction
2.2 DNA alkylation by nitrogen mustards and cytotoxicity mechanisms
2.3 Structure-activity relationships in nitrogen mustards
2.4 Site-directed 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
10.1 Platinum complexes
10.2 Ruthenium complexes
10.3 Miscellaneous metallodrugs
11 Miscellaneous alkylating and acylating antitumor agents
References
Chapter 6 Anticancer drugs that interact with the DNA minor groove
1 Introduction
2 Netropsin, distamycin and related compounds
3 Mitomycins
4 Tetrahydroisoquinoline alkaloids
4.1 Saframycins, bioxalomycin
4.2 Ecteinascidins and analogs
5 Cyclopropylindole alkylating agents
6 Irofulven
7 Pyrrolo[1,4]benzodiazepines
References
Chapter 7 DNA intercalation and topoisomerase inhibition
1 DNA intercalation and its consequences
2 Monofunctional intercalating agents
2.1 Ellipticine and its analogs
2.2 Actinomycins
2.3 Fused quinolines
2.4 Naphthalimides and related compounds
2.5 Chartreusin, elsamicin A and related compounds
2.6 Other monofunctional intercalating agents
3 Bifunctional intercalating agents
4 Indirect DNA damage by DNA topoisomerase inhibitors
4.1 Topoisomerase I mechanism
4.2 Topoisomerase II mechanism
5 Specific topoisomerase I inhibitors
5.1 Camptothecins
5.2 Noncamptothecin topoisomerase I inhibitors
6 Specific topoisomerase II poisons and inhibitors.
6.1 Topoisomerase II poisons
6.1.1 Acridine derivatives
6.1.2 Anthracyclines and related compounds
6.2 Nonintercalating topoisomerase II poisons
6.2.1 Etoposide and its analogs
6.2.2 Salvicine
6.3 Topoisomerase II catalytic inhibitors
6.3.1 Aclarubicin
6.3.2 Merbarone
6.3.3 Bis(dioxopiperazines)
7 Dual topoisomerase II inhibitors
8 Telomerase inhibitors and other anticancer approaches targeting telomers
8.1 Introduction to telomerases
8.2 Quadruplex nucleic acids as targets for anticancer therapeutics. G-quadruplex ligands
8.3 Inhibitors of telomerase reverse transcriptase (hTERT)
8.4 Inhibitors of the RNA domain template
9 DNA repair inhibitors
References
Chapter 8 Epigenetic therapy of cancer
1 Introduction
2 DNA methylation as an epigenetic target
2.1 Nucleoside inhibitors of DNA methyltransferases
2.2 Nucleoside prodrugs as inhibitors of DNA methyltransferases
2.3 Nonnucleoside inhibitors of DNA methyltransferase
2.4 DNA demethylation
3 Modulation of chromatin-related epigenetic processes
3.1 Introduction
3.2 Inhibitors of Zn-dependent histone deacetylases
3.2.1 Short-chain fatty acids
3.2.2 Hydroxamic acids
3.2.3 Cyclic tetrapeptides
3.2.4 Benzamides and other amides
3.2.5 Thiols and other sulfur compounds
3.2.6 The special role of HDAC inhibitors in prostate cancer
3.3 Modulation of sirtuins (SIRTs)
3.3.1 Relevance of the sirtuins in cancer
3.3.2 Sirtuin inhibitors
3.3.3 Sirtuin inhibitors and p53
3.3.4 Sirtuin activators
3.4 Bromodomain inhibitors
3.5 Regulators of histone methylation
3.5.1 Inhibitors of histone methyltransferases (HMTs)
3.5.2 Lysine-specific demethylases (LSDs or KDMs) and their inhibitors
4 Other aspects of the epigenetic therapy of cancer
4.1 Multitarget epigenetic agents
4.2 RNA epigenetics.