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

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 silic...

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Vydané v:Molecules (Basel, Switzerland) Ročník 28; číslo 2; s. 893
Hlavní autori: 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
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Switzerland MDPI AG 01.01.2023
MDPI
Predmet:
Antineoplastic Agents - pharmacology
Apoptosis
Bioavailability
Breast cancer
Cancer therapies
Cell cycle
Cell growth
Cell Proliferation
Cellular Senescence
Chemotherapy
chronic myeloid leukemia
DNA damage
Drug development
Humans
imidazo[1,2-a]pyridines
K562 Cells
Kinases
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Leukemia, Myeloid
Oxidative Stress
Pyridines - pharmacology
selenide
Senescence
Toxicity
senescence
leukemia
chronic myeloid leukemia
imidazo[1,2-a]pyridines
selenide
oxidative stress
ISSN:1420-3049, 1420-3049
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
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content type line 14
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28020893