Chlorinated withanolides from Withania somnifera

Tong, Xiaoqin; Zhang, Huaping; Timmermann, Barbara N.

doi:10.1016/j.phytol.2011.04.016

Cited by 45 publications

(52 citation statements)

References 22 publications

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“…Our own investigation of selected members of the Solanaceae afforded withanolides 1, 20, and 22 from the aerial parts of Vassobia breviflora [17], withanolides 1, 14, 17, 18, and 24-30 from the leaves of Withania somnifera [28], as well as withanolides 1, 3-6, 9, 12, 13, 15-18, 20-23, and 31-35 from the aerial part of Physalis longifolia [29]. The acetate derivatives 7 and 8 were prepared from withalongolide A 6; compounds 10 and 11 were obtained from withalongolide B 9 while compounds 2 and 19 were derived from withaferin A 1.…”

Section: Resultsmentioning

confidence: 98%

“…Withanolides 13-17 are likely to be artifacts formed during the isolation process. The structures of 1-35 were determined by electrospray ionization-mass spectrometry (ESI-MS) and 2D NMR experiments while those of 5, 6, 9, 13, 19, and 28 [28,29] were confirmed by X-ray crystallographic analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Of these, 29 withanolides (1, 3-6, 9, 12-18, and 20-35) were isolated from the three taxa investigated whereas the remaining six analogues (2, 7, 8, 10, 11, and 19) were prepared from the naturally occurring compounds (1, 6, and 9). In this report, we provide a summary of the withanolide chemistry and anti proliferative results obtained during our studies [17,28,29] and attempt to provide a structure-activity relationship analysis (SARA) in comparison with published data in the literature for other withanolides with antiproliferative activity.…”

Section: Introductionmentioning

confidence: 99%

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Antiproliferative withanolides from the solanaceae: A structure-activity study

Zhang¹,

Samadi²,

Gallagher³

et al. 2012

Planta Med

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As part of our search for bioactive compounds from plant biodiversity, 29 withanolides were recently isolated from three members of the Solanaceae: Physalis longifolia, Vassobia breviflora, and Withania somnifera. Six derivatives were prepared from these naturally occurring withanolides. All compounds were evaluated for in vitro antiproliferative activity against an array of cell lines [melanoma cell lines (B16F10, SKMEL28); human head and neck squamous cell carcinomas (HNSCC) cell lines (JMAR, MDA1986, DR081-1); breast cancer cell line (Hs578T), and non-malignant human cell line (MRC5)]. This led to the discovery of 15 withanolides, with IC 50 values in the range of 0.067−17.4 μM, including withaferin A, withaferin A 4,27-diacetate, 27-O-glucopyranosylwithaferin A, withalongolide H, withalongolide C, withalongolide A, withalongolide A 4,27-diacetate, withalongolide A 4,19,27-triacetate, withalongolide B, withalongolide B 4-acetate, withalongolide B 4,19-diacetate, withalongolide D, withalongolide E, withalongolide G, and 2,3-dihydrowithaferin A 3-O-sulfate. In order to update the growing literature on withanolides and their activities, we summarized the distribution, structural types, and antiproliferative activities for all published withanolides to date. The structure-activity relationship analysis (SARA) confirmed the importance of the presence of a Δ 2 -1-oxo-functionality in ring A, a 5β,6β-epoxy or 5α-chloro-6β-hydroxy grouping in ring B, and nine-carbon side chain with a lactone moiety for cytotoxic activity. Conversely, the SARA indicated that the -OH or -OR groups at C-4, 7, 11, 12, 14, 15, 16, 17, 18, 19, 20, 23, 24, 27, and 28 were not contributors to the observed antiproliferative activity within the systems analyzed.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antiproliferative withanolides from the solanaceae: A structure-activity study

Zhang¹,

Samadi²,

Gallagher³

et al. 2012

Planta Med

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“…a For cell lines used, see text. Withanolides 6,[9][10][11][12][13][14]17,18,20,and 21 were inactive for all cell lines used (IC 50 > 10 μM). …”

Section: ■ Experimental Sectionmentioning

confidence: 92%

“…10 The typical withanolide withaferin A (16) (Figure 1) contains these three moieties and has been shown in vitro and in vivo to suppress the growth of an array of tumor cells, including breast, pancreatic, prostate, lung, leukemia, and head and neck squamous cell carcinoma (HNSCC), by inducing apoptosis, 11 thus possessing potential application as an antiproliferative agent. As part of an ongoing study of withanolides from plant sources, 11,12 a library of 224 native plant extracts from the U.S. Great Plains was evaluated for cytotoxic activities against HNSCC and melanoma cell lines using the MTS viability assay. One of the most promising leads, Physalis longifolia Nutt.…”

mentioning

confidence: 99%

Cytotoxic withanolide constituents of Physalis longifolia

Zhang¹,

Samadi²,

Gallagher³

et al. 2012

Planta Med

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Fourteen new withanolides, 1−14, named withalongolides A−N, respectively, were isolated from the aerial parts of Physalis longifolia together with eight known compounds (15−22). The structures of compounds 1−14 were elucidated through spectroscopic techniques and chemical methods. In addition, the structures of withanolides 1, 2, 3, and 6 were confirmed by X-ray crystallographic analysis. Using a MTS viability assay, eight withanolides (1, 2, 3, 7, 8, 15, 16, and 19) and four acetylated derivatives (1a, 1b, 2a, and 2b) showed potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal fibroblast (MRC-5) cells with IC 50 values in the range between 0.067 and 9.3 μM.C lassically defined withanolides are a group of C 28 ergostane-type steroids with a C-22,26 δ-lactone group, first isolated from the genus Withania. 1 They are present primarily in the Solanaceae family, which includes the genera Acnistus, Datura, Dunalia, Jaborosa, Nicandra, Physalis, Withanolides have attracted interest in recent years mainly due to their exhibition of significant biological activities, inclusive of antimicrobial, antitumor, anti-inflammatory, immunomodulatory, and insect-antifeedant activities. 2,3,6 It has been reported that those withanolides displaying the most promising antitumor characteristics contain an α,β-unsaturated ketone in ring A, a 5β,6β-epoxy group in ring B, and a nine-carbon side chain with an α,β-unsaturated δ-lactone group. 10 The typical withanolide withaferin A (16) (Figure 1) contains these three moieties and has been shown in vitro and in vivo to suppress the growth of an array of tumor cells, including breast, pancreatic, prostate, lung, leukemia, and head and neck squamous cell carcinoma (HNSCC), by inducing apoptosis, 11 thus possessing potential application as an antiproliferative agent. As part of an ongoing study of withanolides from plant sources, 11,12 a library of 224 native plant extracts from the U.S. Great Plains was evaluated for cytotoxic activities against HNSCC and melanoma cell lines using the MTS viability assay. One of the most promising leads, Physalis longifolia Nutt. (Solanaceae), commonly known as "long leaf groundcherry", was subjected to a phytochemical investigation, and the results are presented herein, including the details of the isolation and structure elucidation of 14 new withanolides (1−14), four acetylated derivatives (1a, 1b, 2a, and 2b), and eight known compounds (15−22). Their cytotoxicity was determined against HNSCC (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal fibroblast (MRC-5) cells. This constitutes the first report of a phytochemical and bioactivity study of P. longifolia. ■ RESULTS AND DISCUSSIONThe CH 2 Cl 2 −MeOH (1:1) extract of the aerial parts of the title plant and the EtOAc-soluble and n-BuOH-soluble fractions showed cytotoxicity against the above-mentioned cells with IC 50 values in the range between 0.7 and 9.8 μg/mL using a MTS assay. All ...

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