Syntheses of procyanidin B2 and B3 gallate derivatives using equimolar condensation mediated by Yb(OTf)3 and their antitumor activities.

Synthesis of procyanidin B2 and B3 gallate derivatives, 3-O-gallate, 3"-O-gallate, and 3,3"-di-O-gallate, were synthesized using equimolar condensation mediated by Yb(OTf)3. Synthesized compounds showed significant antitumor effects against human prostate PC-3 cell lines. Their activities were weaker than well-known EGCG and prodelphinidin B3.

Adzuki bean (Vigna angularis) extract reduces amyloid-ß aggregation and delays cognitive impairment in Drosophila models of Alzheimer's disease.

BACKGROUND/OBJECTIVES: Alzheimer's disease is a neurodegenerative disease that induces symptoms such as a decrease in motor function and cognitive impairment. Increases in the aggregation and deposition of amyloid beta protein (Aß) in the brain may be closely correlated with the development of Alzheimer's disease. In this study, the effects of an adzuki bean extract on the aggregation of Aß were examined; moreover, the anti-Alzheimer's activity of the adzuki extract was examined. MATERIALS/METHODS: First, we undertook thioflavin T (ThT) fluorescence analysis and transmission electron microscopy (TEM) to evaluate the effect of an adzuki bean extract on Aß42 aggregation. To evaluate the effects of the adzuki extract on the symptoms of Alzheimer's disease in vivo, Aß42-overexpressing Drosophila were used. In these flies, overexpression of Aß42 induced the formation of Aß42 aggregates in the brain, decreased motor function, and resulted in cognitive impairment. RESULTS: Based on the results obtained by ThT fluorescence assays and TEM, the adzuki bean extract inhibited the formation of Aß42 aggregates in a concentration-dependent manner. When Aß42-overexpressing flies were fed regular medium containing adzuki extract, the Aß42 level in the brain was significantly lower than that in the group fed regular medium only. Furthermore, suppression of the decrease in motor function, suppression of cognitive impairment, and improvement in lifespan were observed in Aß42-overexpressing flies fed regular medium with adzuki extract. CONCLUSIONS: The results reveal the delaying effects of an adzuki bean extract on the progression of Alzheimer's disease and provide useful information for identifying novel prevention treatments for Alzheimer's disease.

Identification and characterization of oligomeric proanthocyanidins with significant anti-cancer activity in adzuki beans (Vigna angularis).

The aim of the present study was to characterize and evaluate the anti-cancer activity of proanthocyanidin-enriched fractions from adzuki beans. For this purpose, we concentrated proanthocyanidins from adzuki beans (Vigna angularis) into five fractions using Amberlite XAD-1180N, Toyopearl HW40F, and Sepacore C-18 reverse-phase flash column chromatography. Proanthocyanidin-enriched fractions were characterized as (epi)catechin hexamer, heptamer, and octamer, epigallocatechin-(epi)catechin pentamer, and epigallocatechin-(epi)catechin hexamer using electrospray ionization time-of-flight mass spectrometry and thiolytic degradation. These fractions showed significant anti-cancer activity against the human PC-3 prostate cancer cell line. They also significantly suppressed the expression of the fatty acid-binding protein 5 gene, which plays critical roles in cell growth and metastasis in prostate cancer.

Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts.

Since procyanidins (oligomeric catechin or epicatechin) were reported to exhibit health benefits, much attention has been paid to the synthesis of these compounds, especially those that are longer than trimers. In the present study, syntheses of cinnamtannin A3 (epicatechin pentamer), A4 (epicatechin hexamer), catechin tetramer, pentamer, arecatannin A2 (epicatechin-epicatechin-epicatechin-catechin) and A3 (epicatechin-epicatechin-epicatechin-epicatechin-catechin) were achieved. The key reaction was a Lewis acid mediated equimolar condensation. The antitumor effects of these synthesized compounds against a human prostate cancer cell line (PC-3) were investigated. Among the tested compounds, cinnamtannin A3, A4 and arecatannin A3, which possess epicatechin oligomers longer than tetramers as the basic scaffold, showed significant activities for suppression of cell growth, invasion and FABP5 (fatty acid-binding protein 5) gene expression. Effects on cell cycle distribution showed that cell cycle arrest in the G2 phase was induced. Furthermore, these epicatechin oligomers suppressed significantly the expression of the cancer-promoting gene, FABP5, which is related to cell proliferation and metastasis in various cancer cells. Interestingly, the suppressive activities were associated with the degree of oligomerization of epicatechin. Thus, synthetic studies clearly demonstrate that epicatechin oligomers longer than trimers have significant anti-tumorigenic activities, but not the catechin counterparts.

Synthesis of Arecatannin A1 from Dimeric Epicatechin Electrophile.

Synthesis of arrecatannin A1 (1) was accomplished from dimeric epicatechin electrophile, which was prepared by Zn(OTf)2 mediated self-condensation, and monomeric catechin nucleophile. The condensation was successfully worked using Yb(OTf)3 as a Lewis acid in good yield.