کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1359643 | 981408 | 2010 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis of structurally simplified analogues of aplidinone A, a pro-apoptotic marine thiazinoquinone Synthesis of structurally simplified analogues of aplidinone A, a pro-apoptotic marine thiazinoquinone](/preview/png/1359643.png)
The synthesis of analogues of aplidinone A (7), a prenylated quinone isolated from the Mediterranean ascidian Aplidium conicum, has been performed. This work not only allowed confirming the structural assignment of aplidinone A, previously made with the support of GIAO shielding calculations, but, above all, made a series of structurally related quinone derivatives (compounds 8–13 and the natural metabolite) available for a screening in vitro for cytotoxic and pro-apoptotic activity and for SAR studies. The study evidenced one of the synthetic analogues (11) as a potent cytotoxic and pro-apoptotic agent against several tumor cell lines which also inhibits the TNFα-induced NF-κB activation in a human leukemia T cell line. This exemplifies the potential of a natural product to qualify as lead structure for medicinal chemistry campaigns, affording simplified analogues with better bioactivity and easier to synthesize.
Structurally simplified analogues (8–13) of aplidinone A (7) have been synthesized. Compound 11 is a potent pro-apoptotic agent which also inhibits the TNFα-induced NF-κB activation in human leukemia T cells.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 2, 15 January 2010, Pages 719–727