title: Hybrid antibiotics - clinical progress and novel designs.
abstract: BACKGROUND
  There is a growing need for new antibacterial agents, but success in development of antibiotics in recent years has been limited. This has led researchers to investigate novel approaches to finding compounds that are effective against multi-drug resistant bacteria, and that delay onset of resistance. One such strategy has been to link antibiotics to produce hybrids designed to overcome resistance mechanisms.
  
  
  METHODS
  The concept of dual-acting hybrid antibiotics was introduced and reviewed in this journal in 2010. In the present review the authors sought to discover how clinical candidates described had progressed, and to examine how the field has developed. In three sections the authors cover the clinical progress of hybrid antibiotics, novel agents produced from hybridisation of two or more small-molecule antibiotics, and novel agents produced from hybridisation of antibiotics with small-molecules that have complementary activity.
  
  
  CONCLUSIONS
  Many key questions regarding dual-acting hybrid antibiotics remain to be answered, and the proposed benefits of this approach are yet to be demonstrated. While Cadazolid in particular continues to progress in the clinic, suggesting that there is promise in hybridisation through covalent linkage, it may be that properties other than antibacterial activity are key when choosing a partner molecule.
authors.affiliation: a Medicinal Chemistry , Evotec (UK) Ltd , Abingdon , UK.
authors.forename: Alastair L
authors.initials: AL
authors.lastname: Parkes
authors.affiliation: a Medicinal Chemistry , Evotec (UK) Ltd , Abingdon , UK.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yule
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; C000591679:cadazolid
keywords: Antibiotic resistance; Cadazolid; clinical progress; dual-action drugs; hybrid antibiotics; multi-targeting