Semisynthesis and screening of a small library of pro-apoptotic squamocin analogues:: Selection and study of a benzoquinone hybrid with an improved biological profile.
Semisynthesis and screening of a small library of pro-apoptotic squamocin analogues:: Selection and study of a benzoquinone hybrid with an improved biological profile.
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DOI：
10.1002/cmdc.200500011
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发表时间：
2006-01-01
期刊：
影响因子：
3.4
通讯作者：
Hocquemiller, Reynald
中科院分区：
文献类型：
--
作者：
Derbre, Severine;Duval, Romain;Hocquemiller, Reynald
Acetogenins of Annonaceae, including squamocin (1), exert spectacular cytotoxicity and the most potent inhibition of NADH:ubiquinone oxidoreductase known so far. Cell death induced by these natural products was identified as apoptosis and was thought to be linked to alterations in mitochondrial function. Quinone-squamocin hybrid compounds were semisynthesized and evaluated for their pro-apoptotic properties with a screening method based on dissipation of the mitochondrial transmembrane potential (Delta psi(m)). Herein, we report a short one-step synthesis of a squamocin carboxylic acid analogue. For the first time on a natural product, the radical decarboxylation and quinone addition reaction has enabled preparation of a library of squamocinquinone hybrids and four other analogues. Squamoquinone, tenfold more potent than squamocin as an inducer of apoptosis, emerged as a promising compound, as it induces apoptosis through a mitochondrial caspase-dependent pathway.
