کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1394328 | 1501154 | 2013 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis, structure activity relationship and mode of action of 3-substitutedphenyl-1-(2,2,8,8-tetramethyl-3,4,9,10-tetrahydro-2H,8H-pyrano[2,3-f]chromen-6-yl)-propenones as novel anticancer agents in human leukaemia HL-60 cells Synthesis, structure activity relationship and mode of action of 3-substitutedphenyl-1-(2,2,8,8-tetramethyl-3,4,9,10-tetrahydro-2H,8H-pyrano[2,3-f]chromen-6-yl)-propenones as novel anticancer agents in human leukaemia HL-60 cells](/preview/png/1394328.png)
A novel class of 3-substitutedphenyl-1-(2,2,8,8-tetramethyl-3,4,9,10-tetrahydro-2H,8H-pyrano[2,3-f]chromen-6-yl)-propenones were designed, synthesized and evaluated for their antiproliferative activity against the human cancer cell lines of diverse origin. Structure activity relationship was elucidated with various substitutions on the benzene ring and these variations significantly affected the potency. Most of the twelve tested compounds inhibited the growth of aggressive cancer cell lines. Moreover, three compounds 4j, 4k and 4l displayed excellent cytotoxic profile by inhibiting >90% cell proliferation in HL-60 and Caco-2 cells at 50 μM concentration. Further studies to elucidate the mode of action revealed that these three compounds induced G0/G1 cell cycle arrest and apoptosis, which was accompanied by loss of mitochondrial membrane potential, DNA fragmentation and nuclear morphology in HL-60 cells.
Figure optionsDownload as PowerPoint slideHighlights
► The ‘enone’ moiety is essential for in vitro biological activity of chalcones.
► Three compounds have a significant activity in HL-60 cell line in micromolar range.
► Electron withdrawing substituents are beneficial in terms of cytotoxicity.
► Significant increase in the G0/G1 and sub-G0/G1 population in cell cycle analysis.
► Flow cytometric studies confirmed their anticancer efficacy.
Journal: European Journal of Medicinal Chemistry - Volume 62, April 2013, Pages 545–555