title: Synthesis, Structure Characterization and Antitumor Activity Study of a New Iron(III) Complex of 5-Nitro-8-hydroxylquinoline (HNOQ).
abstract: A new iron(III) complex (1) of 5-nitro-8-hydroxylquinoline (HNOQ) was synthesized and structurally characterized in its solid state and solution state by IR, UV-Vis, electrospray ionization (ESI)-MS, elemental analysis, conductivity and X-ray single crystal diffraction analysis. The DNA binding study suggested that complex 1 interacted with calf thymus (ct)-DNA mainly via an intercalative binding mode. By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the in vitro cytotoxicity of complex 1, comparing with HNOQ and cisplatin, was screened towards a series of tumor cell lines as well as the normal liver cell line HL-7702. Complex 1 showed higher cytotoxicity towards the tested tumor cell lines but lower cytotoxicity towards HL-7702 than HNOQ, in which the T-24 was the most sensitive cell line for 1. Complex 1 caused G2 phase cell cycle arrest and induced cell apoptosis in T-24 cells in a dose-dependent mode, evidenced by changes in cell morphology. Targeting the mitochondrial pathway due to the redox potential of Fe(III)/Fe(II), the apoptotic mechanism in T-24 cells treated by 1 was investigated by reactive oxygen species (ROS) detection, intracellular [Ca(2+)] measurement and caspase-9 and caspase-3 activity assay. It suggested that complex 1 induced cell apoptosis by triggering the caspase-9 and caspase-3 activation via a mitochondrion-mediated pathway.
authors.affiliation: College of Chemistry and Chemical Engineering, Central South University.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Meng
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Liu
authors.forename: Qi-Pin
authors.initials: QP
authors.lastname: Qin
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: You-Nian
authors.initials: YN
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000737:chemistry*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008968:Molecular Conformation; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: C586937:8-hydroxylquinoline; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D011804:Quinolines; D017382:Reactive Oxygen Species; D004247:DNA; C427203:calf thymus DNA; D007501:Iron; D053148:Caspase 3; D053453:Caspase 9; D002945:Cisplatin; D002118:Calcium