Dataset Information

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand.

ABSTRACT: In this study, 9-anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC) 1 and [Co(phen)2(O2CO)]Cl·6H2O 2 (where phen?=?1,10-phenanthroline) were synthesized. [Co(phen)2(O2CO)]Cl·6H2O 2 was used to produce anhydrous [Co(phen)2(H2O)2](NO3)33. Subsequently, anhydrous [Co(phen)2(H2O)2](NO3)33 was reacted with MeATSC 1 to produce [Co(phen)2(MeATSC)](NO3)3·1.5H2O·C2H5OH 4. The ligand, MeATSC 1 and all complexes were characterized by elemental analysis, FT IR, UV-visible, and multinuclear NMR (1H, 13C, and 59Co) spectroscopy, along with HRMS, and conductivity measurements, where appropriate. Interactions of MeATSC 1 and complex 4 with calf thymus DNA (ctDNA) were investigated by carrying out UV-visible spectrophotometric studies. UV-visible spectrophotometric studies revealed weak interactions between ctDNA and the analytes, MeATSC 1 and complex 4 (Kb?=?8.1?×?105 and 1.6?×?104?M-1, respectively). Topoisomerase inhibition assays and cleavage studies proved that complex 4 was an efficient catalytic inhibitor of human topoisomerases I and II?. Based upon the results obtained from the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay on 4T1-luc metastatic mammary breast cancer cells (IC50?=?34.4?±?5.2??M when compared to IC50?=?13.75?±?1.08??M for the control, cisplatin), further investigations into the molecular events initiated by exposure to complex 4 were investigated. Studies have shown that complex 4 activated both the apoptotic and autophagic signaling pathways in addition to causing dissipation of the mitochondrial membrane potential (??m). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time- and concentration-dependent manner coupled with the ??m, studies implicated the intrinsic apoptotic pathway as the major regulator of cell death mechanism.

SUBMITTER: Beebe SJ

PROVIDER: S-EPMC7053658 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand.

Beebe Stephen J SJ Celestine Michael J MJ Bullock Jimmie L JL Sandhaus Shayna S Arca Jessa Faye JF Cropek Donald M DM Ludvig Tekettay A TA Foster Sydney R SR Clark Jasmine S JS Beckford Floyd A FA Tano Criszcele M CM Tonsel-White Elizabeth A EA Gurung Raj K RK Stankavich Courtney E CE Tse-Dinh Yuk-Ching YC Jarrett William L WL Holder Alvin A AA

Journal of inorganic biochemistry 20191102

In this study, 9-anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC) 1 and [Co(phen)2(O2CO)]Cl·6H2O 2 (where phen = 1,10-phenanthroline) were synthesized. [Co(phen)2(O2CO)]Cl·6H2O 2 was used to produce anhydrous [Co(phen)2(H2O)2](NO3)33. Subsequently, anhydrous [Co(phen)2(H2O)2](NO3)33 was reacted with MeATSC 1 to produce ...[more]

PMID: 31715377

Similar Datasets

Project description:The reactivity of mononuclear metal-hydroperoxo adducts has fascinated researchers in many areas due to their diverse biological and catalytic processes. In this study, a mononuclear cobalt(III)-peroxo complex bearing a tetradentate macrocyclic ligand, [CoIII(Me3-TPADP)(O2)]+ (Me3-TPADP = 3,6,9-trimethyl-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane), was prepared by reacting [CoII(Me3-TPADP)(CH3CN)2]2+ with H2O2 in the presence of triethylamine. Upon protonation, the cobalt(III)-peroxo intermediate was converted into a cobalt(III)-hydroperoxo complex, [CoIII(Me3-TPADP)(O2H)(CH3CN)]2+. The mononuclear cobalt(III)-peroxo and -hydroperoxo intermediates were characterized by a variety of physicochemical methods. Results of electrospray ionization mass spectrometry clearly show the transformation of the intermediates: the peak at m/z 339.2 assignable to the cobalt(III)-peroxo species disappears with concomitant growth of the peak at m/z 190.7 corresponding to the cobalt(III)-hydroperoxo complex (with bound CH3CN). Isotope labeling experiments further support the existence of the cobalt(III)-peroxo and -hydroperoxo complexes. In particular, the O-O bond stretching frequency of the cobalt(III)-hydroperoxo complex was determined to be 851 cm-1 for 16O2H samples (803 cm-1 for 18O2H samples), and its Co-O vibrational energy was observed at 571 cm-1 for 16O2H samples (551 cm-1 for 18O2H samples; 568 cm-1 for 16O22H samples) by resonance Raman spectroscopy. Reactivity studies performed with the cobalt(III)-peroxo and -hydroperoxo complexes in organic functionalizations reveal that the latter is capable of conducting oxygen atom transfer with an electrophilic character, whereas the former exhibits no oxygen atom transfer reactivity under the same reaction conditions. Alternatively, the cobalt(III)-hydroperoxo complex does not perform hydrogen atom transfer reactions, while analogous low-spin Fe(III)-hydroperoxo complexes are capable of this reactivity. Density functional theory calculations indicate that this lack of reactivity is due to the high free energy cost of O-O bond homolysis that would be required to produce the hypothetical Co(IV)-oxo product.

Dataset Information

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand.

Publications

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets