笼状藤黄素药效团模式评估。
Evaluation of the pharmacophoric motif of the caged Garcinia xanthones.
机构信息
Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive MC: 0358, La Jolla, CA 92093-0358, USA.
出版信息
Org Biomol Chem. 2009 Dec 7;7(23):4886-94. doi: 10.1039/b913496d. Epub 2009 Sep 24.
Abstract
The combination of unique structure and potent bioactivity exhibited by several family members of the caged Garcinia xanthones, led us to evaluate their pharmacophore. We have developed a Pd(0)-catalyzed method for the reverse prenylation of catechols that, together with a Claisen/Diels-Alder reaction cascade, provides rapid and efficient access to various caged analogues. Evaluation of the growth inhibitory activity of these compounds leads to the conclusion that the intact ABC ring system containing the C-ring caged structure is essential to the bioactivity. Studies with cluvenone (7) also showed that these compounds induce apoptosis and exhibit significant cytotoxicity in multidrug-resistant leukemia cells. As such, the caged Garcinia xanthone motif represents a new and potent pharmacophore.
摘要
几种笼状藤黄烷酮家族成员所表现出的独特结构和强大的生物活性，促使我们对其药效团进行评估。我们开发了一种钯（0）催化的儿茶酚反式烯丙基化方法，该方法与 Claisen/Diels-Alder 反应级联相结合，可快速有效地获得各种笼状类似物。对这些化合物的生长抑制活性进行评估，得出结论：含有 C 环笼状结构的完整 ABC 环系统对于生物活性至关重要。用 cluvenone（7）进行的研究还表明，这些化合物诱导细胞凋亡，并在多药耐药性白血病细胞中表现出显著的细胞毒性。因此，笼状藤黄烷酮基序代表了一种新的有效药效团。
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