title: α-N-heterocyclic thiosemicarbazone Fe(III) complex: Characterization of its antitumor activity and identification of anticancer mechanism.
abstract: We synthesized an α-N-heterocyclic thiosemicarbazone ligand (L) and its Fe complex (C1) and assessed their chemical and biological properties in order to understand their marked activity. Electrochemical studies and ascorbate oxidation studies demonstrated that C1 shows considerable redox activity, and Fe(III/II) redox potentials was within the range accessible to cellular oxidants and reductants. Absorption spectral, emission spectral and viscosity analysis reveal that L and C1 interacted with DNA through intercalation and C1 exhibited a higher DNA binding ability. Agarose gel electrophoresis experiments indicated that C1 exhibited the highest pBR322 DNA cleaving ability. In vitro, C1 showed significantly more anticancer activity than the ligand alone. Moreover, C1 induces production of reactive oxygen species (ROS) and DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the S phase, and mitochondria-mediated apoptosis by regulating the expression of Bcl-2 family proteins.
authors.affiliation: School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gou
authors.affiliation: School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
authors.forename: Shifang
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nantong University, Nantong, Jiangsu, China. Electronic address: fyang@mailbox.gxnu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D013882:Thiosemicarbazones / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D008024:Ligands; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D004247:DNA; D007501:Iron; D001205:Ascorbic Acid
keywords: Anticancer activity; Anticancer mechanism; DNA cleavage; Iron(III) complex; α−N−heterocyclic thiosemicarbazone