Dihydrobenzofuran Neolignanamides: Laccase-Mediated Biomimetic Synthesis and Antiproliferative Activity

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• 作者：Nunzio Cardullo ; Luana Pulvirenti ; Carmela Spatafora ; Nicolò Musso ; Vincenza Barresi ; Daniele Filippo Condorelli ; Corrado Tringali
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：August 26, 2016
• 年：2016
• 卷：79
• 期：8
• 页码：2122-2134
• 全文大小：599K
• 年卷期：0
• ISSN：1520-6025

文摘

The biomimetic synthesis of a small library of dihydrobenzofuran neolignanamides (the natural trans-grossamide (4) and the related compounds 21–28) has been carried out through an eco-friendly oxidative coupling reaction mediated by Trametes versicolor laccase. These products, after complete spectroscopic characterization, were evaluated for their antiproliferative activity against Caco-2 (colon carcinoma), MCF-7 (mammary adenocarcinoma), and PC-3 (prostate cancer) human cells, using an MTT bioassay. The racemic neolignamides (±)-21 and (±)-27, in being the most lipophilic in the series, were potently active, with GI₅₀ values comparable to or even lower than that of the positive control 5-FU. The racemates were resolved through chiral HPLC, and the pure enantiomers were subjected to ECD measurements to establish their absolute configurations at C-2 and C-3. All enantiomers showed potent antiproliferative activity, with, in particular, a GI₅₀ value of 1.1 μM obtained for (2R,3R)-21. The effect of (±)-21 on the Caco-2 cell cycle was evaluated by flow cytometry, and it was demonstrated that (±)-21 exerts its antiproliferative activity by inducing cell cycle arrest and apoptosis.