Details

Autor(en) / Beteiligte

• Zhang, Shixuan
• Ma, Jigang
• Bao, Yongming
• Yang, Puwen
• Zou, Liang
• Li, Kangjian
• Sun, Xiaodan

Titel

Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: Synthesis, SAR analysis, and biological activity

Ist Teil von

• Bioorganic & medicinal chemistry, 2008-08, Vol.16 (15), p.7127-7132

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• Synthesis and structure–activity relationship of nitrogen-containing flavonoid analogues as CDK1/Cyclin B inhibitors are reported. 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-4 H-chromen-4-one 3a, 5,6,7-trihydroxy-8-(pyrrolid inylmethyl)-2-phenyl-4 H-chromen-4-one 3b, and 5,6,7-trihydroxy-8-(piperidinylmethyl)-2-phenyl-4 H-chromen-4-one 3c (IC 50 1.05–1.28 μM) were about sixfold more potent than baicalein 2 (IC 50 6.53 μM). 5,6,7-Trihydroxy-8-(morpholinomethyl)-2-phenyl-4 H-chromen-4-one 3d, 5,6,7-trihydroxy-8-(thiomorpholinomethy)-2-phenyl-4 H-chrom en-4-one 3e, and 5,6,7-trihydroxy-8-(4-methylpiperazinylmethyl)-2-phenyl-4 H-chromen-4-one 3f (IC 50 0.27–0.38 μM) were about 20-fold more potent than baicalein, and were at the same level as flavopiridol (IC 50 0.33 μM).