Document Type

Article

Publication Date

2020

Publication Title

Journal of Inorganic Biochemistry

Volume

203

Pages

58 pp.

DOI

10.1142/S0217751X20300021

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)3 3. Subsequently, anhydrous [Co(phen)2(H2O)2] (NO3)3 3 was reacted with MeATSC 1 to produce [Co(phen)2(MeATSC)](NO3)3·1.5H2O·C2 H5OH 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 IIα. 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 μM when compared to IC50 = 13.75 ± 1.08 μM 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 (ΔΨ m). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time- and concentration-dependent manner coupled with the ΔΨ m , studies implicated the intrinsic apoptotic pathway as the major regulator of cell death mechanism.

Comments

NOTE: This is the author’s post-print version of a work that was published in Journal of Inorganic Biochemistry. The final version was published as:

Beebe, S. J., Celestine, M. J., Bullock, J. L., Sandhaus, S., Arca, J. F., Cropek, D. M., . . . Holder, A. A. (2020). Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand. Journal of Inorganic Biochemistry, 203, 58 pp. doi:10.1016/j.jinorgbio.2019.110907

Available at: http://dx.doi.org/10.1016/j.jinorgbio.2019.110907

Original Publication Citation

Beebe, S. J., Celestine, M. J., Bullock, J. L., Sandhaus, S., Arca, J. F., Cropek, D. M., . . . Holder, A. A. (2020). Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand. Journal of Inorganic Biochemistry, 203, 58 pp. doi:10.1016/j.jinorgbio.2019.110907

ORCID

0000-0002-6075-9452 (Bebee), 0000-0002-0272-5625 (Tano)

Available for download on Tuesday, November 02, 2021

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