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

Imidazo[1,2 ]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...

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Published in:	Molecules (Basel, Switzerland) Vol. 28; no. 2; p. 893
Main Authors:	Burkner, Gabriella Teles, Dias, Dhébora Albuquerque, Souza, Kamylla Fernanda Souza de, Araújo, Anna Júlia Papa de, Basilio, Denise Caroline Luiz Soares, Jacobsen, Fernanda Tondello, Moraes, Ana Carolina Rabello de, Silva-Filho, Saulo Euclides, Cavalcante, Marcos Filipe de Oliveira, Moraes, Cassio Augusto de Oliveira, Saba, Sumbal, Macedo, Maria Lígia Rodrigues, Paredes-Gamero, Edgar Julian, Rafique, Jamal, Parisotto, Eduardo Benedetti
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 16-01-2023 MDPI
Subjects:	Antineoplastic Agents - pharmacology Apoptosis Bioavailability Breast cancer Cancer therapies Carcinogens Cell cycle Cell death Cell growth Cell Proliferation Cellular Senescence Chemotherapy Chronic myeloid leukemia Cytotoxicity DNA damage Drug development Humans imidazo[1,2-a]pyridines K562 Cells Kinases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy Leukemia, Myeloid Lipid peroxidation Lipids Monocytes Myeloid leukemia Oxidants Oxidative Stress Oxidizing agents Peroxidation Pyridines Pyridines - pharmacology Reproductive system selenide Senescence Toxicity senescence leukemia chronic myeloid leukemia imidazo[1,2-a]pyridines selenide oxidative stress
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Summary:	Imidazo[1,2 ]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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1420-3049 1420-3049
DOI:	10.3390/molecules28020893