کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1356720 | 981151 | 2008 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: Synthesis, SAR analysis, and biological activity Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: Synthesis, SAR analysis, and biological activity](/preview/png/1356720.png)
A series of nitrogen-containing flavonoid analogues were designed and synthesized by Mannich reaction, and screened for the inhibitory activities of cyclin-dependent kinases using a FRET-based biochemical assay method. The results showed that C-8 nitrogen-containing baicalein analogues 3a–3f exhibited potent CDK1/Cyclin B inhibitory activities. 5,6,7-Trihydroxy-8-(dimethylaminomethyl)-2-phenyl-4H-chromen-4-one 3a, 5,6,7-trihydroxy-8-(pyrrolid inylmethyl)-2-phenyl-4H-chromen-4-one 3b, and 5,6,7-trihydroxy-8-(piperidinylmethyl)-2-phenyl-4H-chromen-4-one 3c (IC50 1.05–1.28 μM) were about sixfold more potent than baicalein 2 (IC50 6.53 μM). 5,6,7-Trihydroxy-8-(morpholinomethyl)-2-phenyl-4H-chromen-4-one 3d, 5,6,7-trihydroxy-8-(thiomorpholinomethy)-2-phenyl-4H-chrom en-4-one 3e, and 5,6,7-trihydroxy-8-(4-methylpiperazinylmethyl)-2-phenyl-4H-chromen-4-one 3f (IC50 0.27–0.38 μM) were about 20-fold more potent than baicalein, and were at the same level as flavopiridol (IC50 0.33 μM).
Synthesis and structure–activity relationship of nitrogen-containing flavonoid analogues as CDK1/Cyclin B inhibitors are reported.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 15, 1 August 2008, Pages 7127–7132