Date of this Version
2-1-2020
Document Type
Article
Rights
default
Abstract
In this study, 9-anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC) 1 and [Co(phen)(OCO)]Cl·6HO 2 (where phen = 1,10-phenanthroline) were synthesized. [Co(phen)(OCO)]Cl·6HO 2 was used to produce anhydrous [Co(phen)(HO)](NO)3. Subsequently, anhydrous [Co(phen)(HO)](NO)3 was reacted with MeATSC 1 to produce [Co(phen)(MeATSC)](NO)·1.5HO·CHOH 4. The ligand, MeATSC 1 and all complexes were characterized by elemental analysis, FT IR, UV-visible, and multinuclear NMR (H, C, and Co) 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 (K = 8.1 × 10 and 1.6 × 10 M, 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 (IC = 34.4 ± 5.2 μM when compared to IC = 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). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time- and concentration-dependent manner coupled with the ΔΨ, studies implicated the intrinsic apoptotic pathway as the major regulator of cell death mechanism.
DOI
10.1016/j.jinorgbio.2019.110907
Identifier
31715377
Recommended Citation
Beebe SJ, Celestine MJ, Bullock JL, Sandhaus S, Arca JF, Cropek DM, Ludvig TA, Foster SR, Clark JS, Beckford FA, Tano CM, Tonsel-White EA, Gurung RK, Stankavich CE, Tse-Dinh YC, Jarrett WL, Holder AA. Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand. J Inorg Biochem. 2020 Feb;203:110907. doi: 10.1016/j.jinorgbio.2019.110907. Epub 2019 Nov 2. PMID: 31715377; PMCID: PMC7053658.
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Comments
J Inorg Biochem. Author manuscript; available in PMC 2020 Mar 3. Published in final edited form as: J Inorg Biochem. 2020 Feb; 203: 110907. Published online 2019 Nov 2. doi: 10.1016/j.jinorgbio.2019.110907