Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli 'Federico II', Via D. Montesano 49, 80131 Napoli, Italy.
Bioorg Med Chem. 2010 Jan 15;18(2):719-27. doi: 10.1016/j.bmc.2009.11.063. Epub 2009 Dec 6.
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 TNFalpha-induced NF-kappaB 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.
已经完成了从地中海海鞘 Aplidium conicum 中分离出的 prenylated quinone aplidinone A（7）类似物的合成。这项工作不仅证实了 aplidinone A 的结构分配，这是以前在 GIAO 屏蔽计算的支持下完成的，而且还提供了一系列结构相关的醌衍生物（化合物 8-13 和天然代谢物），可用于体外筛选细胞毒性和促凋亡活性以及 SAR 研究。该研究表明，其中一种合成类似物（11）是一种针对多种肿瘤细胞系的有效细胞毒性和促凋亡剂，它还可以抑制人白血病 T 细胞系中 TNFalpha 诱导的 NF-kappaB 激活。这说明了天然产物作为药物化学研究的先导结构的潜力，提供了具有更好生物活性和更易合成的简化类似物。
