New insights into aminoglycoside antibiotics and derivatives.
In the post-genome era, RNA has emerged as a valid molecular target involved in many biochemical pathways such as cellular protein interactions. This includes transcription and translation, HIV-Rev and HIV-tat proteins binding to HIV RNA that encode HIV genetic information. The binding of natural and synthetic aminoglycosides to RNA or RNA-protein complexes has been a central focus of small molecules-RNA recognition events, since they bind selectively to a variety of RNA targets. The understanding of the contribution of shape-based and charge motifs involved in aminoglycosides-RNA complexes gives remarkable information of the translational miscoding process, thereby opening new insights for drug discovery. This review comprises relevant information about aminoglycosides antibiotics, including chemical structure, molecular mechanism, structure-activity relationships, recent advances in aminoglycoside mimetics over the last four years, resistance mechanisms and structure-toxicity relationships.
Silva
Julierme G
JG
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Monte Alegre, 14040-903, Ribeirão Preto-SP, Brazil.
Carvalho
Ivone
I
D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D002240:Carbohydrate Sequence; D004352:Drug Resistance, Microbial; D006801:Humans; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents