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• W3204709708 endingPage "113908" @default.
• W3204709708 startingPage "113908" @default.
• W3204709708 abstract "Highly efficacious and tolerable agents for the treatment of glioblastoma (GBM), the most common and aggressive primary brain tumor, are urgently needed. Herein, we reveal the design, synthesis and biological evaluation of several piperazine based benzamide derivatives, which are based on the non-classical isostere principle and combination principle for GBM therapy. After structure-activity relationship (SAR) study, compound L19 was demonstrated as the most promising compound with IC50 values of 0.15 μM, 0.29 μM, 1.25 μM against GBM C6, U87-MG, U251 cells, respectively. Moreover, compound L19 could inhibit the proliferation, migration and invasion, as well as induce apoptosis and cell cycle arrest of GBM cell lines in vitro. From mechanism perspective, compound L19 could regulate the cell cycle-related proteins and influence the p16INK4a-CDK4/6-pRb pathway by western blotting experiment. What is worth mentioning is that compound L19 could penetrate the blood-brain barrier (BBB) with an exceptional brain-to-plasma ratio of 1.07 in vivo. Besides, the superior anti-glioblastoma potency in vivo of compound L19 was identified on U87-MG-xenograft model without any apparent host toxicity. Overall, the potential of compound L19 warrants further pre-clinical investigation for GBM therapy." @default.
• W3204709708 created "2021-10-11" @default.
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• W3204709708 date "2022-01-01" @default.
• W3204709708 modified "2023-09-24" @default.
• W3204709708 title "Novel piperazine based benzamide derivatives as potential anti-glioblastoma agents inhibiting cell proliferation and cell cycle progression" @default.
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• W3204709708 doi "https://doi.org/10.1016/j.ejmech.2021.113908" @default.
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• W3204709708 hasPublicationYear "2022" @default.
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