Selenylated imidazo[1,2-a]pyridine induces cell senescence and oxidative stress in chronic myeloid leukemia cells

Gabriella Teles Burkner; 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; Sumbal Saba; Maria Lígia Rodrigues Macedo; Edgar Julian Paredes-Gamero1; Jamal Rafique; Eduardo Benedetti Parisotto

doi:10.20944/preprints202211.0410.v1

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preprints.org > chemistry and materials science > medicinal chemistry > doi: 10.20944/preprints202211.0410.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Selenylated imidazo[1,2-a]pyridine induces cell senescence and oxidative stress in chronic myeloid leukemia cells

Gabriella Teles Burkner

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

Sumbal Saba

Maria Lígia Rodrigues Macedo

Edgar Julian Paredes-Gamero1

Jamal Rafique

^* ,

Eduardo Benedetti Parisotto

Version 1 : Received: 18 November 2022 / Approved: 22 November 2022 / Online: 22 November 2022 (07:49:44 CET)

A peer-reviewed article of this Preprint also exists.

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

Abstract

Imidazo[1,2-a]pyridines have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of imidazo[1,2-a]pyridine derivatives by screening its ability as a pro-oxidant. Imidazo[1,2-a]pyridine 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 imidazo[1,2-a]pyridine 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 hours. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress as 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 leu-kemia.

Subject

Chemistry and Materials Science, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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