title: Necroptosis-inducing rhenium(V) oxo complexes.
abstract: Rhenium(V) oxo complexes of general formula [ReO(OMe)(N^N)Cl2], where N^N = 4,7-diphenyl-1,10-phenanthroline, 1, or 3,4,7,8-tetramethyl-1,10-phenanthroline, 2, effectively kill cancer cells by triggering necroptosis, a non-apoptotic form of cell death. Both complexes evoke necrosome (RIP1-RIP3)-dependent intracellular reactive oxygen species (ROS) production and propidium iodide uptake. The complexes also induce mitochondrial membrane potential depletion, a possible downstream effect of ROS production. Apparently, 1 and 2 are the first rhenium complexes to evoke cellular events consistent with programmed necrosis in cancer cells. Furthermore, 1 and 2 display low acute toxicity in C57BL/6 mice and reasonable stability in fresh human blood.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Kogularamanan
authors.initials: K
authors.lastname: Suntharalingam
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Awuah
authors.forename: Peter M
authors.initials: PM
authors.lastname: Bruno
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Johnstone
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Yao-Rong
authors.initials: YR
authors.lastname: Zheng
authors.forename: Julia E
authors.initials: JE
authors.lastname: Page
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hemann
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004355:Drug Stability; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009336:Necrosis / Q000139:chemically induced; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D010618:Phenanthrolines / Q000737:chemistry*; D044463:Receptor, PAR-1 / Q000378:metabolism; D012211:Rhenium / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010618:Phenanthrolines; D044463:Receptor, PAR-1; D016159:Tumor Suppressor Protein p53; D012211:Rhenium; C025205:1,10-phenanthroline