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 byTrametes versicolor laccase. These products, after complete spectroscopic characterization, were evaluated for theirantiproliferative 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 wereresolved through chiral HPLC, and the pure enantiomers were subjected to ECD measurements to establish their absoluteconfigurations at C-2 and C-3. All enantiomers showed potent antiproliferative activity, with, in particular, a GI50 value of 1.1 μMobtained for (2R,3R)-21. The effect of (±)-21 on the Caco-2 cell cycle was evaluated by flow cytometry, and it was demonstratedthat (±)-21 exerts its antiproliferative activity by inducing cell cycle arrest and apoptosis.
|Titolo:||Dihydrobenzofuran Neolignanamides: Laccase-Mediated Biomimetic Synthesis and Antiproliferative Activity|
CARDULLO, NUNZIO (Primo)
TRINGALI, Corrado (Ultimo)
|Data di pubblicazione:||2016|
|Appare nelle tipologie:||1.1 Articolo in rivista|