Aminoglycoside Antibiotics

ISBN-13: 9783642685811 / Angielski / Miękka / 2011 / 372 str.

Irving R. Hooper;Y. Ito;T. Koeda

Opis

The first useful antibiotic found by screening was streptomycin. The late Prof. WAKSMAN started screening for antibacterial antibiotics in 1940 and, after finding actinomycin in 1941, he and his collaborators discovered streptomycin in 1944. This antibiotic made a great contribution in saving human lives from tuberculosis and acute serious infections. About 1957, after wide usage of such antibiotics as penicillin, streptomycin, chloramphenicol, tetracycline, and erythromycin, staphy- lococci and Gram negative organisms resistant to all or most antibiotic drugs ap- peared in hospital patients. The origin and treatment of such resistant strains be- came a major topic of investigation. At that time, kanamycin was discovered and used in the treatment of resistant infections. It may be said that the appearance of resistant strains stimulated a resurgence of research on new antibacterial antibiot- ics and their derivatives. In 1965, kanamycin-resistant strains were found in hospital patients and, undertaking the study of the mechanisms of resistance, I found that resistant strains produce intracellular enzymes that can transfer either the terminal phos- phate of ATP or the acetate of acetyl-CoA to the 3' -hydroxyl or the 6' -amino group of 2-deoxystreptamine~containing antibiotics. These results, reported in 1967, made it possible to design new synthetic derivatives that would inhibit the growth of kanamycin resistant strains of microorganisms. Thus, a new research area was opened: the development of aminoglycosides useful in the treatment of drug-resis- tant infections.

Spis treści

1 The Naturally Occurring Aminoglycoside Antibiotics.- A. Introduction.- B. Aminoglycoses and Noncyclitol Aminoglycosides.- I. Aminoglycose Derivatives.- II. Disaccharides and Pseudodisaccharides.- III. Trisaccharides.- C. Aminocyclitol Aminoglycosides Containing Streptamine, 2-Deoxystreptamine, or Their Derivatives.- I. Monosubstituted Streptamine and 2-Deoxystreptamine Aminoglycosides.- 1. 4- or 6-Substituted Cyclitol.- 2. 5-Substituted Cyclitol.- II. Disubstituted 2-Deoxystreptamine Aminoglycosides.- 1. 4,5-Disubstituted Cyclitol.- 2. 4,6-Disubstituted Cyclitol.- III. 1-N-Acyl Substituted Cyclitol.- D. Aminoglycosides with Cyclitol Aglycones Other than Streptamine or 2-Deoxystreptamine.- I. Nonbasic Cyclitol.- II. Monoaminocyclitol.- III. Diaminocyclitol.- References.- 2 Total Synthesis and Chemical Modification of the Aminoglycoside Antibiotics.- A. Introduction.- B. Several Reactions and Methods Generally Useful for the Synthesis of Aminoglycoside Antibiotics.- I. Simultaneous Protection of Vicinal Trans-Equatorial Amino and Hydroxyl Groups.- II. Selective Cyclic Acetalation.- III. 1,2-cis-Glycosylation of Aminosugars.- IV. Selective Deoxygenation Reactions.- 1. 3-Deoxygenation.- 2. 3,4-Dideoxygenation.- V. Selective N-Protection via Temporary Metal Chelation of Vicinal and Nonvicinal Amino-Hydroxy or Amino-Amino Groups.- VI. Determination of the Configurations of Aminopyranosides and Aminocyclitols by the Shift in Optical Rotation Due to Copper(II) Chelate Formation.- C. Total Synthesis and Modification of Aminoglycoside Antibiotics.- I. Streptomycin Group.- 1. Total Synthesis of Streptomycin and Dihydrostreptomycin.- 2. Chemical Modification of Streptomycin and Dihydrostreptomycin.- II. Pseudodisaccharides Containing 4-Substituted 2-Deoxystreptamine — Paromamine, Neamine, and Related Compounds.- 1. Synthesis of Paromamine and Neamine.- 2. Deoxygenated Derivatives.- 3. Epimerized Derivatives.- 4. Amino-Deoxy Derivatives.- 5. Derivatives Having a Side Chain or Longer Chain.- 6. 1-N-Acyl Derivatives.- 7. Other Derivatives.- III. Pseudotrisaccharides Containing 4,5-Disubstituted 2-Deoxystreptamine — Ribostamycin, Butirosins, and Related Compounds.- 1. Synthesis of Ribostamycin and Related Pseudotrisaccharides.- 2. Deoxy Derivatives.- 3. 1-N-Acyl and 1-N-Alkyl Derivatives of 4,5-Disubstituted Pseudotrisaccharides.- IV. Pseudotetra- and Pseudopentasaccharides Containing 4,5-Disubstituted 2-Deoxystreptamine — Neomycins, Paromomycins, Lividomycins, and Related Compounds.- 1. Total Synthesis of Neomycin C.- 2. Synthesis of Analogs of Neomycin, Paromomycin, and Lividomicin B.- 3. Amino-Deoxy Derivatives.- 4. N-Alkyl Derivatives.- 5. 1-N-Acyl Derivatives.- V. Pseudotrisaccharides Containing 4,6-Disubstituted 2-Deoxystreptamine — Kanamycin, Tobramycin, Gentamicin, and Related Compounds.- 1. Kanamycins and Their Derivatives.- 2. Gentamicins and Related Compounds.- 3. Sisomicin, Its Derivatives, and Related Unsaturated Compounds.- 4. 1-N-Acylgentamicins and 1-N-Acylsisomicins.- 5. Seldomycin Modifications.- 6. Other 4,6-Disubstituted Derivatives.- VI. Other Groups.- 1. Kasugamycin and Its Modifications.- 2. Spectinomycin Group.- 3. Fortimicins, Istamycins, and Related Compounds.- 4. Sorbistins and Analogs.- 5. Minosaminomycin.- 6. Alpha,Alpha-Trehalosamine.- References.- 3 Biosynthesis and Mutasynthesis of Aminoglycoside Antibiotics.- A. Introduction.- I. Historical Background.- II. Methodology.- 1. Application of Labeled Compounds.- 2. Application of Cell-Free Extracts of Mycelia or Enzymes.- 3. Application of Mutants.- III. Plasmid Involvement.- 1. General Aspects.- 2. Plasmid Involvement in Aminoglycoside Synthesis.- 3. Experimental Methods.- B. Biosynthesis of Major Aminoglycosides.- I. Streptomycin and Bluensomycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Correlation with Cell Wall Biosynthesis.- 4. Plasmid Involvement.- II. Neomycin and Paromomycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Plasmid Involvement.- III. Ribostamycin, Xylostasin, and Butirosin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Glucosamine Auxotroph and Butirosin Biosynthesis.- 4. Plasmid Involvement.- IV. Kanamycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Plasmid Involvement.- V. Gentamicin and Sisomicin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- VI. Spectinomycin (Actinospectacin).- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- VII. Kasugamycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Plasmid Involvement.- VIII. Validamycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- IX. Miscellaneous Aminoglycosides.- 1. 1,4-Diaminocyclitol Aminoglycosides.- 2. Monoaminocyclitol Aminoglycosides.- 3. Apramycin.- X. Comprehensive Discussion on the Biosynthesis of Aminoglycosides.- C. Mutational Biosynthesis (Mutasynthesis).- D. Conclusion.- References.- 4 Antibacterial Activity of Aminoglycoside Antibiotics.- A. Introduction.- B. Drug Resistance Plasmids.- I. The Discovery of R Factors.- II. The Discovery of Nonconjugative Resistance (r) Plasmids.- C. Resistance Patterns of Bacteria.- D. Bacterial Strains Resistant to Aminoglycoside Antibiotics.- I. Drug Resistance Mediated by R Plasmids.- II. Antibacterial Activity of Aminoglycoside Antibiotics.- E. Conclusion.- References.- 5 Mechanism of Action of Aminoglycoside Antibiotics.- A. The Effects on Bacterial Cells and Their Components.- I. In vivo Effects on Bacteria in Relation to Mode of Action.- II. Interference with Protein Synthesis in vitro.- III. Localization of Drug Sensitivity, Resistance, and Dependence on the Ribosome.- IV. Interaction with Ribosomes and Ribosomal Components.- 1. Binding of Streptomycin to the Ribosome and Ribosomal Subunits.- 2. Binding Site of Streptomycin on the Ribosome.- 3. Binding of Kanamycin to the Ribosome and Ribosomal Subunits.- 4. Binding of Other Aminoglycosides to the Ribosome and Ribosomal Subunits.- V. Interference with Ribosomal Functions.- 1. Inhibition of Initiation of Protein Synthesis.- 2. Chain Elongation Processes Affected.- 3. Interference with Termination.- VI. Interaction with Bacterial Cell Envelope.- 1. Membrane Damage.- 2. Uptake of Streptomycin by Bacterial Cells.- 3. Drug Resistance Due to Transport Barriers.- VII. Structure-Activity Relationships.- 1. Structure Required for Codon Misreading Activity.- 2. Structure Needed for the Inhibition of Translocation.- B. Effects on Mammalian or Eukaryotic Cells and Their Components.- I. Interaction with Ribosomes and Interference with Ribosomal Functions.- II. Interaction with Tubulin and Microtubules.- III. Interaction with Actin.- IV. Interaction with Membrane or Phospholipid.- C. Peptide Antibiotics Showing Similar Mechanisms of Inhibition of Ribosomal Functions.- I. Viomycin.- 1. Inhibition of Protein Synthesis.- 2. Binding to Ribosomes and Ribosomal Subunits.- 3. Localization of Drug Resistance in the Ribosome.- 4. Mechanism of Translocation Inhibition.- II. Negamycin.- D. Discussion.- E. Summary.- I. Localization of Drug Sensitivity, Resistance, and Dependence on the Ribosome.- II. Binding of Aminoglycosides to the Ribosome.- III. Inhibition of Initiation of Protein Synthesis.- IV. Stimulation of Codon Misreading.- V. Interference with Aminoacyl-tRNA Binding.- VI. Inhibition of Translocation of Peptidyl-tRNA.- VII. Interference with Termination of Protein Synthesis.- VIII. The Effects on Cell Membrane.- IX. Uptake of Aminoglycosides by Bacterial Cells.- X. Effects on Mammalian or Eukaryotic Cell Components.- References.- 6 Mechanisms of Resistance to Aminoglycoside Antibiotics.- A. Introduction.- B. Biochemical Mechanisms of Resistance.- I. Discovery of Enzymes Involved in Resistance.- II. Resistance to 2-Deoxystreptamine-Containing Antibiotics.- 1. 3?-Phosphotransferase [APH (3?)].- 2. 5?-Phosphotransferase [APH (5?)].- 3. 2?-Phosphotransferase [APH (2?)].- 4. 2?-Adenylyltransferase [AAD (2?)].- 5. 4?-Adenylyltransferase [AAD (4?)].- 6. 6?-Acetyltransferase [AAC (6?)].- 7. 3-Acetyltransferase [AAC (3)].- 8. 2?-Acetyltransferase [AAC (2?)].- III. Resistance to Streptomycins.- 1. 3?-Adenylyltransferase [AAD (3?)].- 2. 3?-Phosphotransferase [APH (3?)].- 3. 6-Adenylyltransferase [AAD (6)] and 6-Phosphotransferase [APH (6)].- IV. Resistance to Fortimicins.- V. Immobilization of Enzymes.- VI. Structural Elucidation of Modified Antibiotics by Spectrometry.- VII. Similarity to Enzymes Involved in Biosynthesis.- C. Derivatives Active Against Resistant Strains.- D. Conclusion.- References.- 7 Toxicology and Pharmacology of Aminoglycoside Antibiotics.- A. Introduction.- B. Nephrotoxicity of Aminoglycosides.- I. Nephrotoxicity of Individual Aminoglycosides.- II. Intensification of Nephrotoxicity of Aminoglycosides by Concomitant Use with Other Drugs.- III. Reduction of Nephrotoxicity of Aminoglycosides by Concomitant Use of Other Drugs.- IV. Experimental Methods for Investigating Nephrotoxicity.- 1. Determination of Lysozyme.- 2. Determination of Alanine Aminopeptidase (AAP) Activity.- 3. Determination of N-Acetyl-?-D-Glucosaminidase (NAG)Activity.- 4. Determination of ?2-Microglobulin.- C. Ototoxicity of Aminoglycosides.- I. Effects of Cochlear Hair Cells.- II. Effects on Vestibular Organs.- III. Ototoxicity by Concomitant Use of Aminoglycosides with Other Drugs.- IV. Correlation Between Renal Toxicity and Ototoxicity of Aminoglycosides.- V. Transfer Routes of Aminoglycosides into the Inner Ear Fluids.- VI. Fetal Ototoxicity of Aminoglycosides.- D. Acute Lethal Toxicity of Aminoglycosides.- E. Correlation Between Chemical Structure and LD50 Values of Aminoglycosides.- I. Kanamycin Group.- II. Gentamicin Group.- III. Neomycin Group.- IV. Ribostamycin Group.- F. General Pharmacology of Aminoglycosides.- I. Effect on Neuromuscular Junctions.- II. General Pharmacologic Actions, Especially on Smooth Muscle and Cardiovascular System.- G. Pharmacokinetics.- I. Recent Progress in Assay Methods for Aminoglycosides in Serum and Other Body Fluids.- 1. Microbiologic Assay.- 2. Radioimmunoassay.- 3. High-Performance Liquid Chromatography (HPLC).- 4. Enzymatic Assay.- II. Pharmacokinetics of Aminoglycosides.- 1. Compartment Models for Pharmacokinetic Analysis and Calculation of Parameters.- 2. Pharmacokinetic Parameters in Normal Animals.- 3. Pharmacokinetic Parameters in Human with Normal Renal Function.- 4. Relationship Between Serum Level, Acute Toxicity, and Mode of Administration in Experimental Animals.- III. Metabolism and Excretion.- 1. Metabolism.- 2. Excretion.- IV. Tissue Distribution.- 1. Tissue Distribution in Animals.- 2. Tissue Distribution in Humans.- V. Accumulation in Kidneys.- 1. Renal Accumulation in Animals.- 2. Renal Accumulation in Humans.- VI. Binding to Biopolymers.- 1. Binding to Heparin.- 2. Binding to Serum Proteins.- VII. Relationship Between Renal Function and Pharmacokinetics: Clinical Applications.- References.