کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1392812 1501161 2012 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cell death triggered by synthetic flavonoids in human leukemia cells is amplified by the inhibition of extracellular signal-regulated kinase signaling
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Cell death triggered by synthetic flavonoids in human leukemia cells is amplified by the inhibition of extracellular signal-regulated kinase signaling
چکیده انگلیسی

A new class of methyl esters of flavonoids, with different substituents on the B ring were synthesized and evaluated for their antiproliferative activity against the human leukemia cell line HL-60. The presence of either a methyl group (1f) or a chlorine atom (1o) at position 2′ of the B ring played an important role in affecting antiproliferative activity. The cytotoxic effects of these compounds were accompanied by the concentration- and time-dependent appearance of DNA- and nuclear-fragmentation, increase in the percentage of sub-G1 cells, and processing of multiple caspases and poly(ADP-ribose)polymerase cleavage. Pretreatment of cells with the specific mitogen-activated extracellular kinases (MEK) 1/2 inhibitor PD98059, together with 1f and 1o, resulted in an important enhancement of cell death, which might have clinical implications for the use of both compounds in combination with MEK 1/2 inhibitors as potential therapeutic agents.

Figure optionsDownload as PowerPoint slideHighlights
► New methyl esters of flavone-8-carboxylic acid analogs were synthesized.
► Two selected methyl esters display cytotoxic activities in human leukemia cells.
► These flavones induce apoptosis and processing of multiple caspases.
► Apoptosis is enhanced by the inhibition of mitogen-activated extracellular kinases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 55, September 2012, Pages 284–296
نویسندگان
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