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Article

Selenylated Imidazo[1,2-a]pyridine Induces Cell Senescence and Oxidative Stress in Chronic Myeloid Leukemia Cells

by
Gabriella Teles Burkner
1,
Dhébora Albuquerque Dias
1,
Kamylla Fernanda Souza de Souza
2,
Anna Júlia Papa de Araújo
1,
Denise Caroline Luiz Soares Basilio
1,
Fernanda Tondello Jacobsen
3,
Ana Carolina Rabello de Moraes
3,
Saulo Euclides Silva-Filho
1,
Marcos Filipe de Oliveira Cavalcante
4,
Cassio Augusto de Oliveira Moraes
5,
Sumbal Saba
4,
Maria Lígia Rodrigues Macedo
1,
Edgar Julian Paredes-Gamero
1,2,
Jamal Rafique
4,5,* and
Eduardo Benedetti Parisotto
1,*
1
Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil
2
Department of Biochemistry, Federal University of São Paulo, São Paulo 4044-020, Brazil
3
Department of Clinical Analysis, Center for Health Sciences, Federal University of Santa Catarina, Florianópolis 88040-970, Brazil
4
Institute of Chemistry (IQ), Federal University of Goiás (UFG), Goiania 74690-900, Brazil
5
Institute of Chemistry (INQUI), Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79074-460, Brazil
*
Authors to whom correspondence should be addressed.
Molecules 2023, 28(2), 893; https://doi.org/10.3390/molecules28020893
Submission received: 17 November 2022 / Revised: 24 December 2022 / Accepted: 13 January 2023 / Published: 16 January 2023
(This article belongs to the Special Issue Chalcogens in Medicinal Chemistry)
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Abstract

Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.
Keywords: leukemia; imidazo[1,2-a]pyridines; selenide; oxidative stress; senescence; chronic myeloid leukemia leukemia; imidazo[1,2-a]pyridines; selenide; oxidative stress; senescence; chronic myeloid leukemia
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MDPI and ACS Style

Burkner, G.T.; Dias, D.A.; Souza, K.F.S.d.; Araújo, A.J.P.d.; Basilio, D.C.L.S.; Jacobsen, F.T.; Moraes, A.C.R.d.; Silva-Filho, S.E.; Cavalcante, M.F.d.O.; Moraes, C.A.d.O.; et al. Selenylated Imidazo[1,2-a]pyridine Induces Cell Senescence and Oxidative Stress in Chronic Myeloid Leukemia Cells. Molecules 2023, 28, 893. https://doi.org/10.3390/molecules28020893

AMA Style

Burkner GT, Dias DA, Souza KFSd, Araújo AJPd, Basilio DCLS, Jacobsen FT, Moraes ACRd, Silva-Filho SE, Cavalcante MFdO, Moraes CAdO, et al. Selenylated Imidazo[1,2-a]pyridine Induces Cell Senescence and Oxidative Stress in Chronic Myeloid Leukemia Cells. Molecules. 2023; 28(2):893. https://doi.org/10.3390/molecules28020893

Chicago/Turabian Style

Burkner, Gabriella Teles, Dhébora Albuquerque Dias, Kamylla Fernanda Souza de Souza, Anna Júlia Papa de Araújo, Denise Caroline Luiz Soares Basilio, Fernanda Tondello Jacobsen, Ana Carolina Rabello de Moraes, Saulo Euclides Silva-Filho, Marcos Filipe de Oliveira Cavalcante, Cassio Augusto de Oliveira Moraes, and et al. 2023. "Selenylated Imidazo[1,2-a]pyridine Induces Cell Senescence and Oxidative Stress in Chronic Myeloid Leukemia Cells" Molecules 28, no. 2: 893. https://doi.org/10.3390/molecules28020893

APA Style

Burkner, G. T., Dias, D. A., Souza, K. F. S. d., Araújo, A. J. P. d., Basilio, D. C. L. S., Jacobsen, F. T., Moraes, A. C. R. d., Silva-Filho, S. E., Cavalcante, M. F. d. O., Moraes, C. A. d. O., Saba, S., Macedo, M. L. R., Paredes-Gamero, E. J., Rafique, J., & Parisotto, E. B. (2023). Selenylated Imidazo[1,2-a]pyridine Induces Cell Senescence and Oxidative Stress in Chronic Myeloid Leukemia Cells. Molecules, 28(2), 893. https://doi.org/10.3390/molecules28020893

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