Efficient synthesis of substituted 7-methyl-2H,5H-pyrano[4,3-b]pyran-5-ones and evaluation of their in vitro antiproliferative/cytotoxic activities

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• 作者：Heiko Leutbecher ; Lawrence A.D. Williams ; Harald Rö ; sner ; Uwe Beifuss
• 关键词：Heterocycles ; Domino reaction ; Cytotoxicity ; Apoptosis ; Substituent effects
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 February 2007
• 卷：17
• 期：4
• 页码：978-982
• 文件大小：374 K

摘要

Substituted 7-methyl-2H,5H-pyrano[4,3-b]pyran-5-ones and related heterocycles 3 were synthesized through an efficient domino Knoevenagel condensation/6π-electron electrocyclization. In vitro antiproliferative/cytotoxic activity evaluation was performed with human SH-SY5Y neuroblastoma cells and revealed IC₅₀ values ranging from 6.7 to >200 μM. The compound that was most cytotoxic to the neuroblastoma cells, that is, 2-isobutyl-3-isopropyl-7-methyl-2H,5H-pyrano[4,3-b]pyran-5-one (3a), also exhibited necrotic effects on the human IPC melanoma cells.