Synthesis and antiproliferative evaluation of amide-containing flavone and isoflavone derivatives

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• 作者：I-Li Chen ; Jhy-Yih Chen ; Po-Chuen Shieh ; Jih-Jung Chen ; Choa-Hsun Lee ; Shin-Hun Juang ; Tai-Chi Wang
• 关键词：Antiproliferative activity ; Cytotoxicity ; Apoptosis ; Flavone ; Isoflavone
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：15 August 2008
• 年：2008
• 卷：16
• 期：16
• 页码：7639-7645
• 全文大小：414 K

文摘

Certain amide-containing flavone and isoflavone derivatives were synthesized and evaluated for their antiproliferative activities. These compounds were synthesized via alkylation of hydroxyl precursors followed by the reaction with H₂SO₄ and NaN₃ (Schmidt reaction).

The preliminary assays indicated that the inhibitory activity against the growth of NCI-H661 decreased in an order of linked chromophore flavone-6-yl 16a–d > flavone-7-yl 17a–d > flavone-3-yl 15a–d and isoflavone-7-yl 18a–d. Among these flavone-6-yl derivatives, N-(4-methoxyphenyl)-2-(4-oxo-2-phenyl-4H-chromen-6-yloxy)acetamide (16c) was the most potent with a GI₅₀ value of 0.84 μM. The inhibitory activity against the growth of NPC-TW01 decreased in an order of linked chromophore flavone-6-yl 16a–d > isoflavone-7-yl 18a–d > flavone-7-yl 17a–d > flavone-3-yl 15a–d. Flavone-6-yl derivatives 16a–d demonstrated significant inhibitory activities against the growth of NPC-TW01 cell with an average GI₅₀ value of 0.84 μM. The oxime derivatives 1 and 2 caused accumulation of NPC-TW01 cell in G₂/M phase which were distinct from that of their amide isomers 16b and 16c, respectively, which induced cell-cycle arrest in G₀/G₁ phase followed by apoptosis. Therefore, the antiproliferative mechanism of flavone derivatives was affected not only by the phenyl benzopyran-4-one pharmacophore but also by the peripheral substituents.