Development of Aminoglycoside Antibiotics Effective Against Resistant Bacterial Strains

Lin      Yang; Xin-Shan      Ye

doi:10.2174/156802610793176684

Abstract

Aminoglycosides are important broad-spectrum antibiotics used in the therapy of many microbial infections. As the bacterial resistance to antibiotic therapy is appearing as an increasingly significant threat to public health, the development of aminoglycoside antibiotics with extended antibacterial spectrum and potency, devoid of nephro- and ototoxicity, and evading the resistance process returns to the focus of researchers. In this review, various developments brought to the aminoglycoside family of antibiotics effective against resistant bacteria have been described, focused on chemical modifications, drug-modifying enzyme inhibitors, and conformationally constrained analogs, as well as related antibacterial compounds, with the hope to provide information useful in rational design of novel antibiotics addressing bacterial resistance, and paving the way for new perspectives in antimicrobial therapy.

Keywords: Aminoglycoside antibiotics, drug-modifying enzymes, bacterial resistance, inhibitor, antimicrobial activity, Aminoglycoside, broad-spectrum antibiotics, antimicrobial therapy, Gram-negative, Gram-positive, aminocyclitol, glycosidic linkage, 2-deoxystreptamine, streptidine ring, spectinomycin, Mycobacterium tuberculosis, neomycin, pa-ramomycin, kanamycins, tobramycin, gentamicins, semi-synthetic derivatives amikamycin, dibekacin, sisomicin, netilmicin, Ototoxicity, 16S rRNA, phosphotransferases, adenyltransferases, acetyltrans-ferases, Anti-APH(3')s, Aminoglycoside 3'-phosphotransferases, Gram-negative APH(3'), neomycin B, anti-anthrax drugs, Anti-APH(2'')/AAC(6'), methicillin-resistant Staphylococcus aureus, O-acetyltransfer, N-acetyltransfer, Arbekacin, aminoglycoside-modifying, 5-deoxy-5-episubstituted arbekacin derivatives, 5-deoxy-5-epiamino-ABK, aminoglycoside-modifying enzyme, resistance nodulation division, tetraazidoneamine, ribostamycin and pyranmycin, pSF815 plasmid, acetyl coenzyme A, synthetic AAC(6') in-hibitors, pyrophosphate group, structure-activity relationships, ANT (2'') Inhibitors, aminoglycoside-resistant bacteria, APH Inhibitors, nucleophilic amino acid side chain, protein kinases, acetyltransferases, nucleo-tidyltransferases, sulfotransferases, X-ray crystallography, paromomycin, Dimeric Derivatives, hydroxyamine motif, Hoog-steen face, neamine dimers, vancomycin-resistant enterococci, fluoroquinolone- ciprofloxacin, DNA gyrase, topoisomerase, Cipro-NeoB hybrids, C16 or C20 fatty acid, multidrug resistant, 3,5-diamino-piperidinyl triazines, Neamine-derived pseudodisaccharides, Non-Carbohydrate Inhibitors of AGMEs, bovine antimicrobial peptide indolicidin