title: Supramolecular iron cylinder with unprecedented DNA binding is a potent cytostatic and apoptotic agent without exhibiting genotoxicity.
abstract: The supramolecular iron cylinder, [Fe(2)L(3)]Cl(4) (L = C(25)H(20)N(4)), shows unprecedented DNA binding in vitro, inducing intramolecular DNA coiling and also targeting Y-shaped DNA junctions. We investigated its effects on proliferation and survival in both tumor and normal cell lines. Iron cylinder reduced mitochondrial activity of cultures with potency similar to cisplatin, inhibited the cell cycle, and increased cell death by apoptosis. Associated with this, we observed a lowering of the association of propidium iodide with cellular DNA consistent with an observed competitive displacement of PI from naked DNA by cylinders. Importantly, and in contrast to existing anticancer drugs such as cisplatin, the iron cylinder [Fe(2)L(3)](4+) was not genotoxic. In summary, the design of metal complexes such as [Fe(2)L(3)](4+) with potential anticancer properties in the absence of genotoxicity may represent a significant step toward therapeutic advancement.
authors.affiliation: School of Chemistry, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Anna C G
authors.initials: AC
authors.lastname: Hotze
authors.forename: Nikolas J
authors.initials: NJ
authors.lastname: Hodges
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Hayden
authors.forename: Carlos
authors.initials: C
authors.lastname: Sanchez-Cano
authors.forename: Christopher
authors.initials: C
authors.lastname: Paines
authors.forename: Natalia
authors.initials: N
authors.lastname: Male
authors.forename: Man-Kit
authors.initials: MK
authors.lastname: Tse
authors.forename: Chris M
authors.initials: CM
authors.lastname: Bunce
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Chipman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hannon
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008928:Mitochondria / Q000187:drug effects; D008958:Models, Molecular; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000628:therapy*
chemical_list: D054697:Cytostatic Agents; D005296:Ferrous Compounds; D004247:DNA; D002945:Cisplatin