دورية أكاديمية
Selenylated Imidazo[1,2 -a ]pyridine Induces Cell Senescence and Oxidative Stress in Chronic Myeloid Leukemia Cells.
العنوان: | Selenylated Imidazo[1,2 -a ]pyridine Induces Cell Senescence and Oxidative Stress in Chronic Myeloid Leukemia Cells. |
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المؤلفون: | Burkner GT; Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil., Dias DA; Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil., Souza KFS; Department of Biochemistry, Federal University of São Paulo, São Paulo 4044-020, Brazil., Araújo AJP; Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil., Basilio DCLS; Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil., Jacobsen FT; Department of Clinical Analysis, Center for Health Sciences, Federal University of Santa Catarina, Florianópolis 88040-970, Brazil., Moraes ACR; Department of Clinical Analysis, Center for Health Sciences, Federal University of Santa Catarina, Florianópolis 88040-970, Brazil., Silva-Filho SE; Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil., Cavalcante MFO; Institute of Chemistry (IQ), Federal University of Goiás (UFG), Goiania 74690-900, Brazil., Moraes CAO; Institute of Chemistry (INQUI), Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79074-460, Brazil., Saba S; Institute of Chemistry (IQ), Federal University of Goiás (UFG), Goiania 74690-900, Brazil., Macedo MLR; Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil., Paredes-Gamero EJ; Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil.; Department of Biochemistry, Federal University of São Paulo, São Paulo 4044-020, Brazil., Rafique J; Institute of Chemistry (IQ), Federal University of Goiás (UFG), Goiania 74690-900, Brazil.; Institute of Chemistry (INQUI), Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79074-460, Brazil., Parisotto EB; Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Brazil. |
المصدر: | Molecules (Basel, Switzerland) [Molecules] 2023 Jan 16; Vol. 28 (2). Date of Electronic Publication: 2023 Jan 16. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, c1995- |
مواضيع طبية MeSH: | Leukemia, Myeloid* , Antineoplastic Agents*/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/drug therapy, Humans ; Apoptosis ; Oxidative Stress ; Cell Proliferation ; Cellular Senescence ; Pyridines/pharmacology ; K562 Cells |
مستخلص: | 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. |
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معلومات مُعتمدة: | 315399/2020-1, 422645/2021-4, 309975/2022-0, and 403210/2021-6 National Council for Scientific and Technological Development; Call No. 01/2022, No.: 210, and Call No. 01/2022, No.: 223 Fundação de Apoio a Pesquisa do Estado de Goiás; 001 Coordenação de Aperfeicoamento de Pessoal de Nível Superior |
فهرسة مساهمة: | Keywords: chronic myeloid leukemia; imidazo[1,2-a]pyridines; leukemia; oxidative stress; selenide; senescence |
المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Pyridines) |
تواريخ الأحداث: | Date Created: 20230121 Date Completed: 20230124 Latest Revision: 20230201 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC9860887 |
DOI: | 10.3390/molecules28020893 |
PMID: | 36677949 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1420-3049 |
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DOI: | 10.3390/molecules28020893 |