Unusually sulfated and oxygenated steroids from Withania somnifera

Misra, Laxminarain; Lal, Payare; Sangwan, Rajender S.; Sangwan, Neelam S.; Uniyal, G. C.; Tuli, Rakesh

doi:10.1016/j.phytochem.2005.10.001

Cited by 80 publications

(36 citation statements)

References 12 publications

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“…Glucosylation of sterol is catalyzed by sterol glucosyltransferase. Withasteroids are glucosylated sterols (Mishra et al 2005). One member of 3β-hydroxy sterol glucosyltransferase (SGT) gene family was cloned recently from W. somnifera (Sharma et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Metabolic shift from withasteroid formation to phenylpropanoid accumulation in cryptogein-cotransformed hairy roots of Withania somnifera (L.) Dunal

et al. 2014

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Cotransformed hairy roots containing a gene that encodes a fungal elicitor protein, β-cryptogein, were established in Withania somnifera, a medicinal plant widely used in Indian systems of medicine. To find out whether β-cryptogein protein endogenously elicits the pathway of withasteroid biosynthesis, withaferin A and withanolide A contents along with transcript accumulation of farnesyl pyrophosphate (FPP) synthase, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), and sterol glycosyltransferase (SGT) were analyzed in both cryptogein-cotransformed and normal hairy roots of W. somnifera. It was observed that the withaferin A and withanolide A contents were drastically higher in normal hairy roots than cryptogein-cotransformed ones. Similar trends were also observed on the levels of transcript accumulation. Subsequently, the enzyme activity of phenylalanine ammonia lyase (PAL), one of the key enzymes of phenylpropanoid pathway, was measured in both cryptogein-cotransformed and normal hairy roots of W. somnifera along with the levels of PAL transcript accumulation. Upliftment of PAL activity was observed in cryptogein-cotransformed hairy roots as compared to the normal ones, and the PAL expression also reflected a similar trend, i.e., enhanced expression in the cryptogein-cotransformed lines. Upliftment of wall-bound ferulic acid accumulation was also observed in the cryptogein-cotransformed lines, as compared to normal hairy root lines. Thus, the outcome of the above studies suggests a metabolic shift from withanolide accumulation to phenylpropanoid biosynthesis in cryptogein-cotransformed hairy roots of W. somnifera.

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Section: Discussionmentioning

confidence: 99%

Metabolic shift from withasteroid formation to phenylpropanoid accumulation in cryptogein-cotransformed hairy roots of Withania somnifera (L.) Dunal

et al. 2014

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“…Withasomniferol B (16) is a stereoisomer of the known ixocarpanolide, although the configurations at positions 24 and 25 were not specified. Hydration of the 2,3-double bond was found in compounds 20 (11), 21, and 22 (12), and the latter was isolated as the 3-sulfate, an unusual feature in withanolides (see Sect. 4.2.5.).…”

Section: B6b-epoxywithanolides and Related Compoundsmentioning

confidence: 97%

Withanolides and Related Steroids

Misico

Nicotra

Oberti

et al. 2011

Progress in the Chemistry of Organic Natural Products Vol. 94

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“…Besides withanolides 7 and 19, there are only five other 3-O-sulfate withanolides previously reported from Datura metel, 33 Solanum cilistum, 34 and Withania somnifera. 35 All the withanolides (1−21) and the four acetylated derivatives (1a, 1b, 2a, and 2b) were tested against the HNSCC (JMAR, MDA-1986), melanoma (B16F10 and SKMEL-28), and/or normal fetal fibroblast (MRC-5) cells for their cytotoxicity. As summarized in Table 6, withanolides 1−5, 7, 8, 15, 16, and 19 and the four derivatives (1a, 1b, 2a, and 2b) showed cytotoxic effects against the cells tested with IC 50 values in the range 0.067−9.3 μM, while the other withanolides were inactive.…”

Section: Journal Of Natural Productsmentioning

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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Unusually sulfated and oxygenated steroids from Withania somnifera

Cited by 80 publications

References 12 publications

Metabolic shift from withasteroid formation to phenylpropanoid accumulation in cryptogein-cotransformed hairy roots of Withania somnifera (L.) Dunal

Metabolic shift from withasteroid formation to phenylpropanoid accumulation in cryptogein-cotransformed hairy roots of Withania somnifera (L.) Dunal

Withanolides and Related Steroids

Cytotoxic withanolide constituents of Physalis longifolia

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