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• W4206981191 endingPage "105591" @default.
• W4206981191 startingPage "105591" @default.
• W4206981191 abstract "In this study, three novel sets of 4-aryl-4H-chromene derivatives 4a-c, 6a-d and 7a-c were synthesized and evaluated for anticancer activity. Characterization of new compounds was established on basis of elemental analyses and spectral data. All new compounds were investigated for their antiproliferative activity against HCT-116, HepG-2 and MCF-7 cell lines using vinblastine and staurosporine as positive controls. Compounds 4b, 4c and 6d showed superior cytotoxicity against HCT-116, HepG-2 and MCF-7 cell lines, respectively with IC50 ranged from 3.31 to 4.95 μM. Additionally, compound 4b showed excellent cytotoxic activity (IC50 = 39.83 μM) against resistant HCT-116 better than doxorubicin (IC50 = 164.60 μM), while compounds 4c and 6d exhibited moderate cytotoxic activity against resistant HepG-2 and resistant MCF-7 cell lines. The most potent compounds inhibited both β-tubulin polymerization (IC50 = 8.78 - 16.47 μM) and c-Src kinase (IC50 = 0.07 - 0.18 μM) enzymes. Compounds 4b, 4c and 6d activated caspase-3, caspase-7, and caspase-9 proteins relative to untreated cells, revealing apoptosis induction. Apoptosis was also confirmed through up-regulation of Bax and down-regulation of Bcl-2 protein expression levels. Cell cycle analysis of compound 6d showed accumulation of cells in pre-G1 phase and cell cycle arrest at S phase in MCF-7 treated cells. As well 6d caused 7- and 63- fold increase in apoptotic cell population at early and late apoptosis stages. Finally, molecular modeling study was performed to predict the binding pattern of the target compounds inside c-Src kinase receptor." @default.
• W4206981191 created "2022-01-26" @default.
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• W4206981191 date "2022-03-01" @default.
• W4206981191 modified "2023-10-16" @default.
• W4206981191 title "Characterization of novel heterocyclic compounds based on 4-aryl-4H-chromene scaffold as anticancer agents: Design, synthesis, antiprofilerative activity against resistant cancer cells, dual β-tubulin/c-Src inhibition, cell cycle arrest and apoptosis induction" @default.
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• W4206981191 doi "https://doi.org/10.1016/j.bioorg.2021.105591" @default.
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