Doxorubicin

Doxorubicin: Anticancer Antibiotics details the development of doxorubicin as a wide-spectrum antitumor antibiotic. The book begins by tracing the discovery and development of doxorubicin, highlighting factors such as (a) the involvement of organic chemistry at an early stage, which allowed the rapid identification of doxorubicin and ensured its prompt availability for the clinical trials; (b) the well-established, pioneering expertise in experimental chemotherapy of Professor Aurelio di Marco and his group at Istituto Nazionale Tumori, Milan; and (c) the highly motivated interest of experienced clinicians. The remaining chapters provide an overview of basic studies in the area of medicinal chemistry and related fields that have resulted from doxorubicin development. Such studies have been concerned with both biochemical and biophysical investigations at the molecular level and at different levels of biological organization. A large body of work aimed at developing synthetic procedures for the drug and for new related analogs of potential clinical usefulness has also been carried out.

PrefaceAcknowledgments1 Discovery and Development of Doxorubicin Antitumor Activity of an Anthracycline Pigment Anthracyclines and Anthracyclinones: The First Decade Daunorubicin The Isolation of Doxorubicin The Structure and Stereochemistry of Doxorubicin Antitumor Activity on Experimental Tumors Clinical Activity of Doxorubicin Analytical Development and Synthesis of Radiolabeled Doxorubicin Conjugates and Complexes of Doxorubicin as Antitumor Agents References2 Total Synthesis of Doxorubicin and Related Compounds Wong's Synthesis of Daunomycinone Other Syntheses Starting from 3-Methoxyphthalate and a Tetralin or Their Equivalents Closure of Ring A in Substituted Anthraquinones and Their Derivatives Applications of the Diels - Alder Reaction for the Construction of Ring A Other Syntheses Based on Diels-Alder Condensation Syntheses Based on Different Principles The Carbohydrate Moiety Other Studies Related to Ring A Functionalization References3 Molecular Interactions X-Ray Diffraction Studies Association and Dissociation Equilibria in Solution Oxidoreduction Behavior Complexes with Metal Ions The DNA Intercalation Complex Protein Binding Phospholipids Mucopolysaccharides Effect of Respiratory Processes in Subcellular Preparations Interference with Redox Reactions and Formation of Radicals Inhibition of (Na+ + K+) ATPase and of Ion Transport in Subcellular Preparations References4 Studies with Living Systems Uptake and Distribution in Cultured Sensitive Cells Effects of DNA-Related Cell Functions in Vitro Other Studies in Cultured Cells Studies with Resistant Cells Studies with Cultured Heart Cells Metabolism Pharmacokinetics Pharmacological Properties in Whole Mammalian Systems References5 Analogues Modified in Ring A Substitution Derivatization at C-13 and C-14 Side-Chain Oxidative Degradation Modifications at C-9 and C-10 Substitution at C-8 4-Demethoxy-7,10-Ethanodaunomycinone References6 Analogues Modified in the Aminosugar Residue The L-Arabino Analogues and the Development of 4'-Epidoxorubicin Other Analogues Modified at C-4' Other Configurational Analogues Other Functional Analogues Disaccharides Amides N,N-Dimethyldaunorubicin Nonsugar Derivatives References7 Analogues Modified in the Anthraquinone Chromophore Synthesis of 4-Demethoxydaunorubicins Properties of 4-Demethoxydaunorubicins Other Synthetic Approaches to 4-Demethoxy Analogues New Ring D-Substituted 4-Demethoxydaunorubicins and 4-Demethoxydoxorubicins Replacement of 4-O-Methyl and Other Alkyl Groups The 6-O-Methyl and 11-O-Methyl Derivatives 5-Iminodaunorubicin Recent Developments References8 New Developments in Biosynthetic Anthracyclines The Rhodomycins and Related Compounds Pyrromycinone and Aklavinone Glycosides Biosynthetic Glycosides Related to Daunorubicin Other Anthracycline Antibiotics The Biosynthesis of the Anthracyclines Microbial Transformations ReferencesIndex