受生物启发的苯并[k,l]呫吨木脂素：合成、DNA相互作用及抗增殖特性
Bio-inspired benzo[k,l]xanthene lignans: synthesis, DNA-interaction and antiproliferative properties.
作者信息
Spatafora Carmela, Barresi Vincenza, Bhusainahalli Vedamurthy M, Di Micco Simone, Musso Nicolò, Riccio Raffaele, Bifulco Giuseppe, Condorelli Daniele, Tringali Corrado
机构信息
Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
出版信息
Org Biomol Chem. 2014 May 7;12(17):2686-701. doi: 10.1039/c3ob42521e.
In this work twelve benzo[k,l]xanthene lignans were synthesized by biomimetic, Mn-mediated oxidative coupling of caffeic esters and amides. These compounds, bearing different flexible pendants at position C1/C2 of the aromatic core, interact with DNA in a dual mode, as confirmed by DF-STD NMR analysis and molecular docking: the planar core acts as a base pair intercalant, whereas the flexible pendants act as minor groove binders. Their antiproliferative activity was evaluated on a panel of six tumor cell lines: HT-29, Caco-2, HCT-116 (human colon carcinoma), H226, A549 (human lung carcinoma), and SH-SY5Y (human neuroblastoma). All compounds under study, except 29, resulted in activity against one or more cell lines, and the markedly lipophilic esters 13 and 28 showed the highest activity. Compound 13 was more active than the anticancer drug 5-fluorouracil (5-FU) towards HCT-116 (colon, GI50 = 3.16 μM) and H226 (lung, GI50 = 4.33 μM) cell lines.
在本研究中，通过仿生的、锰介导的咖啡酸酯和酰胺的氧化偶联反应合成了12种苯并[k,l]呫吨木脂素。这些化合物在芳香核的C1/C2位带有不同的柔性侧链，经DF-STD NMR分析和分子对接证实，它们以双重模式与DNA相互作用：平面核心作为碱基对嵌入剂，而柔性侧链作为小沟结合剂。在一组六种肿瘤细胞系上评估了它们的抗增殖活性：HT-29、Caco-2、HCT-116（人结肠癌）、H226、A549（人肺癌）和SH-SY5Y（人神经母细胞瘤）。除29外，所有研究的化合物均对一种或多种细胞系有活性，且显著亲脂的酯13和28表现出最高活性。化合物13对HCT-116（结肠，GI50 = 3.16 μM）和H226（肺，GI50 = 4.33 μM）细胞系的活性高于抗癌药物5-氟尿嘧啶（5-FU）。
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