Seven resveratrol-related monomeric stilbenoids were submitted to biomimetic oxidative coupling in the presence of laccase from Trametes versicolor (TvL), and gave racemic dihydrobenzofuran dehydrodimers (_)-15 to (_)-21. These products, after spectral characterization, were submitted to an antiproliferative activity bioassay against SW480 human colon cancer cells. Five racemates were found to be active, and were resolved by chiral HPLC. The pure enantiomers were subjected to circular dichroism measurements to establish their absolute configurations at C-7 and C-8. These enantiomerically pure compounds were submitted to the anti-proliferative activity assay towards SW480 cells, and were all shown to be active with IC50 values in the approximate range 20–90 μM. In some cases, a significant difference between the activity of the 7R,8R and 7S,8S enantiomers was observed, but a defined configuration of the stereogenic centers does not appear to be a structural requirement for the activity. The comparison between the most active compounds and the inactive ones strongly suggests that the presence of a methoxy group in the position ortho to the C-4 hydroxy group is highly detrimental to the activity.

Resveratrol-related Dehydrodimers: Laccase-mediated Biomimetic Synthesis and Antiproliferative Activity

TRINGALI, Corrado
2012-01-01

Abstract

Seven resveratrol-related monomeric stilbenoids were submitted to biomimetic oxidative coupling in the presence of laccase from Trametes versicolor (TvL), and gave racemic dihydrobenzofuran dehydrodimers (_)-15 to (_)-21. These products, after spectral characterization, were submitted to an antiproliferative activity bioassay against SW480 human colon cancer cells. Five racemates were found to be active, and were resolved by chiral HPLC. The pure enantiomers were subjected to circular dichroism measurements to establish their absolute configurations at C-7 and C-8. These enantiomerically pure compounds were submitted to the anti-proliferative activity assay towards SW480 cells, and were all shown to be active with IC50 values in the approximate range 20–90 μM. In some cases, a significant difference between the activity of the 7R,8R and 7S,8S enantiomers was observed, but a defined configuration of the stereogenic centers does not appear to be a structural requirement for the activity. The comparison between the most active compounds and the inactive ones strongly suggests that the presence of a methoxy group in the position ortho to the C-4 hydroxy group is highly detrimental to the activity.
2012
Medicinal chemistry; Biomimetic synthesis; Enzyme catalysis; Antiproliferation; Antitumor agents; Structure-activity relationships
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/30591
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