Department of Molecular and Agrifood Sciences, Università di Milano, Via Celoria 2, 20133 Milano, Italy.
Bioorg Med Chem. 2011 Aug 15;19(16):4971-84. doi: 10.1016/j.bmc.2011.06.056. Epub 2011 Jul 2.
A novel 5-oxa-6a,8-diazaindeno[2,1-b]phenanthren-7-one scaffold was designed and synthesized as an active analogue of the cytotoxic marine alkaloid Lamellarin D. The design was based on molecular modeling of the site of interaction of Lamellarin D with DNA-topoisomerase I cleavable complex, whereas the synthesis capitalized on a simple Friedel-Crafts cyclization of indole to a β-carbolinone nucleus. The product exhibited topoisomerase I poisoning activity and submicromolar cytotoxicity on human non-small cell lung cancer H460 cell line.
设计并合成了一种新型的 5-氧代-6a,8-二氮杂茚并[2,1-b]菲啶-7-酮骨架，作为细胞毒性海洋生物碱拉米林 D 的活性类似物。该设计基于拉米林 D 与 DNA-拓扑异构酶 I 可切割复合物相互作用位点的分子建模，而合成则利用吲哚的简单 Friedel-Crafts 环化作用生成β-咔啉酮核。该产物表现出拓扑异构酶 I 毒化活性和对人非小细胞肺癌 H460 细胞系的亚微摩尔细胞毒性。
