α-N-heterocyclic thiosemicarbazone Fe(III) complex: Characterization of its antitumor activity and identification of anticancer mechanism.
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.
['Gou|Yi|Y|', 'Wang|Jun|J|', 'Chen|Shifang|S|', 'Zhang|Zhan|Z|', 'Zhang|Yao|Y|', 'Zhang|Wei|W|', 'Yang|Feng|F|']
D000970:Antineoplastic Agents D017209:Apoptosis D001205:Ascorbic Acid D045744:Cell Line, Tumor D004247:DNA D053837:DNA Cleavage D006571:Heterocyclic Compounds D006801:Humans D007501:Iron D008024:Ligands D008958:Models, Molecular D008968:Molecular Conformation D009942:Organometallic Compounds D010084:Oxidation-Reduction D013882:Thiosemicarbazones
Anticancer mechanism Anticancer activity DNA cleavage Iron(III) complex α−N−heterocyclic thiosemicarbazone