Antiproliferative Pterocarpans and Coumestans from Lespedeza bicolor

Abstract

Chromatographic purification of a methanol extract of the roots of Lespedeza bicolor led to the isolation of four new pterocarpans (1− 4), two new coumestans (6 and 7), two new arylbenzofurans (8 and 9), and the known pterocarpan 1-methoxyerythrabyssin II (5). Their structures were identified using NMR spectroscopy, UV spectroscopy, and mass spectrometry. Cytotoxicity assays showed that compounds 1−9 exerted antiproliferative effects on blood cancer cells. Of these compounds, 1 and 6 induced mitochondrial depolarization and induced apoptosis in Jurkat cells. These compounds promoted cell death by inducing cell-cycle arrest at the G1 stage, reducing levels of BCL2, and increasing cleavage of PARP-1. These findings indicate that 1 and 6 are possible lead compounds for the treatment of human leukemia cells via intracellular signaling.Lespedeza bicolor Turcz. plants, of the family Leguminosae, are distributed widely across Eastern North America and Eastern Asia. 1 Plants in the genus Lespedeza have been used traditionally in the treatment of diuresis, skin diseases, cough, and fever. 2,3 Moreover, components from the roots of L. bicolor were reported to inhibit bacterial neuraminidase and cancer cell growth. 4,5 Compounds isolated from L. bicolor include alkaloids, flavonoids, sterols, and terpenenoids, which have been investigated for anti-inflammatory, antioxidative, cytotoxic, and blood glucose-reducing effects. 4−8 Flavonoids predominate in the genus Lespedeza, and several common compounds of this type have been isolated from L. bicolor. 9 Recently, two prenylated isoflavanones and six pterocarpans were purified from the stem bark of L. bicolor, 10 with the six pterocarpans showing inhibitory activity against bacterial neuraminidase. 5 In addition, four other pterocarpans exhibited an antiproliferative effect against cancer cell lines. 11 The present report describes the isolation from the roots of L. bicolor of four new pterocarpans (1−4), two new coumestans (6 and 7), two new arylbenzofurans (8 and 9), and the known pterocarpan 1-methoxyerythrabyssin II (5). 12 Nine isolated compounds (1−9) were analyzed for their potential antileukemic activities in Jurkat leukemia cells. 13 The present study revealed that pterocarpans and coumestans isolated from L. bicolor exerted potent cytotoxic effects, including the induction of apoptosis in Jurkat cells. The induction of apoptosis was investigated by the evaluation of the protein expression of Bcl-2 and cleaved PARP using Western blotting. To elucidate the antioxidant effects of the compounds, the reduction of mitochondrial tetramethylrhod-amine methyl ester (TMRM) and the induction of cell-cycle arrest were evaluated.

Polyphenolic Compounds from Lespedeza Bicolor Root Bark Inhibit Progression of Human Prostate Cancer Cells via Induction of Apoptosis and Cell Cycle Arrest

“…The obtained extract of L. bicolor root bark (1.7 g) was chromatographed on a polyamide column (80 g, 50-160 µm, Sigma-Aldrich, St. Louis, MI, USA). The column was eluted with a hexane-CHCl 3 solution system with gradually increasing CHCl 3 amounts (hexane/CHCl 3 , 1:0, 100:1, 50:1, 40:1) to give fractions 1-13 and then with a CHCl 3 -EtOH solution system with gradually increasing EtOH amounts (CHCl 3 /EtOH, 1:0, 100:1, 50:1, 40:1, v/v) to give fractions [14][15][16][17][18][19][20]. The fractions containing polyphenolic compounds according to TLC HPLC data were subjected to further purification.…”

“…A comparison of the HPLC profiles of L. bicolor stem bark and root bark showed that compounds 7 and 8 are also present in L. bicolor stem bark but in smaller amounts than in root bark (Figure 2). Recently, Korean colleagues isolated five pterocarpans, two new coumestans, and two new arylbenzofurans with prenyl and geranyl substituents in their structures [14]. These isolated compounds contain a methoxy group at C-1 and exhibited antiproliferative effects on human leukemia cells.…”

“…Moreover, PC-3 cells have been reported to be rather resistant to docetaxel, and therefore, are known as one of the most aggressive prostate cancer cell lines used as in vitro and in vivo models. Notably, all eight isolated compounds exhibited a cytotoxic activity in both prostate cancer cell lines in the micromolar range, while non-malignant MRC-9 cells were less affected under Recently, Korean colleagues isolated five pterocarpans, two new coumestans, and two new arylbenzofurans with prenyl and geranyl substituents in their structures [14]. These isolated compounds contain a methoxy group at C-1 and exhibited antiproliferative effects on human leukemia cells.…”

2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from Inula britannica Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells

“…The cells were treated with different concentrations of HEDO (3,5,10,20,50, and 100 µM). Cell viability was assessed using an MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay, as described in a previous paper written by the authors of this study [18].…”

Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran

“…Hydroxylated benzofurans are ubiquitous structural motifs of various natural products and bioactive molecules. [1] As shown in Scheme 1, these molecules contain at least one free hydroxyl group attached to the benzene ring with different substituent patterns,w hich have attracted much attention owing to their wide spectrum of biological activities.F or example,a saphytoestrogen, coumestrol (with one hydroxyl at C6) exhibits diverse activities against cancer,n eurological disorders,a nd autoimmune diseases. [2] Them arine natural product liphagal (with two hydroxyl groups at C5 and C6) can modulate human phosphatidylinositol-3-kinase (PI3K) sig-nalling pathway, [3] which may have therapeutic potential for the treatment of autoimmune disorders,c ardiovascular diseases,a nd cancer.…”