title: The Antibacterial Activity of Metal Complexes Containing 1,10- phenanthroline: Potential as Alternative Therapeutics in the Era of Antibiotic Resistance.
abstract: The "antibiotic era", characterized by the overuse and misuse of antibiotics, over the last half-century has culminated in the present critical "era of resistance". The treatment of bacterial infections is challenging because of a decline in the current arsenal of useful antibiotics and the slow rate of new drug development. The discovery of a new gene (mcr-1) in 2015, which enables bacteria to be highly resistant to polymyxins (such as colistin), the last line of antibiotic defence left, heralds a new level of concern as this gene is susceptible to horizontal gene transfer, with alarming potential to be spread between different bacterial populations, suggesting that the progression from "extensive drug resistance" to "pan-drug resistance" may be inevitable. Clearly there is a need for the development of novel classes of anti-bacterial agents capable of killing bacteria through mechanisms that are different to those of the known classes of antibiotics. 1,10-phenanthroline (phen) is a heterocyclic organic compound which exerts in vitro antimicrobial activity against a broad-spectrum of bacteria. The antimicrobial activity of phen can be significantly modulated by modifying its structure. The development of metal-phen complexes offers the medicinal chemist an opportunity to expand such structural diversity by controlling the geometry and varying the oxidation states of the metal centre, with the inclusion of appropriate auxiliary ligands in the structure, offering the opportunity to target different biochemical pathways in bacteria. In this review, we summarize what is currently known about the antibacterial capability of metal-phen complexes and their mechanisms of action.
authors.affiliation: The Centre for Biomimetic and Therapeutic Research, Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin 8, Ireland.
authors.forename: Livia
authors.initials: L
authors.lastname: Viganor
authors.affiliation: The Centre for Biomimetic and Therapeutic Research, Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin 8, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Howe
authors.affiliation: The Centre for Biomimetic and Therapeutic Research, Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin 8, Ireland.
authors.forename: Pauraic
authors.initials: P
authors.lastname: McCarron
authors.affiliation: Chemistry Department, Maynooth University, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Malachy
authors.initials: M
authors.lastname: McCann
authors.affiliation: College of Sciences and Health, Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Devereux
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D055808:Drug Discovery; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D010618:Phenanthrolines; C025205:1,10-phenanthroline
keywords: 1,10-phenanthroline; Alternative therapeutics; Antibacterial activity; Antibiotic resistance; Metal complexes