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Activity of Nonnucleoside Inhibitors of O6-methylguanine-DNA Methyltransferase Repair Enzyme in Human Cells In Vitro

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Abstract

The repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) eliminates alkyl lesions that play the main anticancer role in alkylating chemotherapy. The inhibition of MGMT leads to increasing effectiveness of alkylating chemotherapy. In this study, new potential MGMT inhibitors were tested. It was found that some compounds demonstrate low cytotoxicity and high effectiveness in human cells in vitro.

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  • 31 January 2024

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Authors and Affiliations

  1. Department of Human Genetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03680, Kyiv, Ukraine

    K. S. Zhuvaka, G. P. Volynets, T. P. Ruban, Z. M. Nidoeva, A. P. Iatsyshyna, L. L. Macewizc, V. G. Bdzhola, S. M. Yarmoluk & L. L. Lukash

Authors
  1. K. S. Zhuvaka
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  2. G. P. Volynets
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  3. T. P. Ruban
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  4. Z. M. Nidoeva
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  5. A. P. Iatsyshyna
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  6. L. L. Macewizc
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  7. V. G. Bdzhola
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  8. S. M. Yarmoluk
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  9. L. L. Lukash
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Corresponding authors

Correspondence to K. S. Zhuvaka, G. P. Volynets, T. P. Ruban, Z. M. Nidoeva, A. P. Iatsyshyna, L. L. Macewizc, V. G. Bdzhola, S. M. Yarmoluk or L. L. Lukash.

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The authors declare that they have no conflicts of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

CONCLUSIONS

In this study we examined a number of compounds for their potential as MGMT inhibitors and assessed their cytotoxicity and effectiveness in vitro. Results indicated that compounds 41 (5-(5-Сhloro-2-hydroxy-benzylidene)-4-thioxo-thiazolidin-2-one), 41B (5-Benzo[1,3]dioxol-5-ylmethylene-thiazolidine-2,4-dione), and 89 (2-[5-(4-Bromo-phenyl)-pyrimidin-4-yl]-5-ethoxy-phenol) showed promising characteristics with lower cytotoxicity and higher effectiveness compared to the standard inhibitor BG at a concentration of 10 µM.

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Zhuvaka, K.S., Volynets, G.P., Ruban, T.P. et al. Activity of Nonnucleoside Inhibitors of O6-methylguanine-DNA Methyltransferase Repair Enzyme in Human Cells In Vitro. Cytol. Genet. 57, 556–566 (2023). https://doi.org/10.3103/S0095452723060105

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