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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Research Article

Cytotoxic Activity of a Unique Monomeric Heterogeneous Two-Coordinate Ligand Monovalent Gold Complex with Tiopronin and a Heterocyclic Mercapto-Tetrazole Compound

Author(s): Naoyuki Sano, Hironori Yoshino, Yoshiaki Sato, Hideo Honma, Christopher E.J. Cordonier and Ikuo Kashiwakura*

Volume 29, Issue 22, 2022

Published on: 11 January, 2022

Page: [3973 - 3982] Pages: 10

DOI: 10.2174/0929867328666211018094206

Price: $65

Abstract

Background: The importance of the role of NF-κB is recognized in situations such as malignant transformation and metastasis of cancer, and it has been suggested that inhibiting this role can be one of the cancer treatment strategies. Gold preparations such as auranofin are known to have an indirect NF-κB inhibitory effect.

Objective: We synthesized a novel gold complex [tiopronin monovalent gold-5-mercapto- 1-methyl tetrazole, abbreviated as TPN-Au(I)-MM4], with different physical properties and chemical structure from auranofin, and evaluated its cytotoxic activity and radiation sensitizing effect on human THP1 cells.

Methods: The number of viable cells was counted by the trypan blue dye exclusion method. The cell death evaluation was performed by FITC-Annexin V+ and PI staining. In investigating the radiation sensitizing effect of TPN-Au(I)-MM4, this compound [10 or 25 μM] was added into the culture medium 1 h before X-ray irradiation.

Results: In the cells treated with 25 μM TPN-Au(I)-MM4 for 72 h, a decrease in the proliferation of THP1 cells was observed [The relative values of viable cells in the control group and the 25 μM treatment group were approximately 6.8 and 4.2, respectively]. In the combination of 25 μM of the compound treatment and X-ray irradiation, an increase of approximately 3.0-fold was observed in 2 Gy irradiation and approximately 1.4-fold in 4 Gy irradiation as in comparison to the case of irradiation alone.

Conclusion: These results suggest that TPN-Au(I)-MM4 reduces the proliferation of THP1 cells through the induction of cell death, and the combined use of TPN-Au(I)-MM4 and X-ray irradiation shows effective cytotoxicity against THP1 cells.

Keywords: Gold complex, tpn-au[I]-mm4, radiation sensitizing effect, human thp1 cells, reduces the proliferation, induction of cell death.

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