New withanolides from Mandragora officinarum: First report of withanolides from the Genus Mandragora

Suleiman, Rami; Zarga, Musa Abu; Sabri, Salim S.

doi:10.1016/j.fitote.2010.05.013

Cited by 16 publications

(12 citation statements)

References 11 publications

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“…2 B shows the occurrence of withanolides or related compounds reported in the literature and of the 24ISO/SSR-like gene in tribes of the Solanaceae family, indicating a correlation between the presence of 24ISO / SSR-like and withanolides or petuniasterones (C 28 isoprenoids found in Petunia ). Withanolides or closely related compounds have been detected in several genera of the Solanoideae subfamily, namely in Acnistus , Brachistus , Deprea , Discopodium , Dunalia , Eriolarynx , Iochroma , Leucophysalis , Physalis , Salpichroa , Tubocapsicum , Vassobia , Withania , and Witheringia from the Physalineae tribe; Datura from the Datureae tribe; Hyoscyamus from the Hyoscyameae tribe; Lycium from the Lycieae tribe; Jaborosa from the Jaboroseae tribe; and Solanum from the Solaneae tribe, as well as the genera Exodeconus , Nicandra , and Mandragora , whose positions are unresolved ( 17 , 18 ).…”

Section: Resultsmentioning

confidence: 99%

Third DWF1 paralog in Solanaceae, sterol Δ ²⁴ -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Knoch

Sugawara

Mori

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceWithanolides form a major class of plant steroids with unique side-chain modifications. Withanolides are one of the main active components in an Indian Ayurvedic medicinal plant, ashwagandha, which has been used for over 3,000 y. Because of their highly diversified structures, withanolides are promising pharmacological compounds with proven antiinflammatory and anticancer properties. We identified a sterol Δ24-isomerase (24ISO) catalyzing the first committed step in the biosynthesis of withanolides and related compounds. Identification of 24ISO paves the way for targeted manipulations to increase withanolide yields and as a starting point to elucidate the downstream pathway of yet-unknown withanolide biosynthesis. This study also demonstrates how the evolution of enzymes catalyzing double-bond modifications of triterpene side chains lead to diversity in structures and functions.

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Section: Resultsmentioning

confidence: 99%

Third DWF1 paralog in Solanaceae, sterol Δ ²⁴ -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Knoch

Sugawara

Mori

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…The unmodified type I withanolides showed more potent cytotoxicity than the other structural types analyzed to date. Based on these observations, it is suggested that the -OH or -OR groups at C-4, 7,11,12,14,15,16,17,18,19,20,23,24, and 27 are non-contributors to the antiproliferative activity. In most cases, withanolides possessing -OH or -OR groups at such positions are slightly less potent than those lacking the -OH or -OR groups.…”

Section: -Oh Groupmentioning

confidence: 99%

“…2), have been reported from various plant sources. As listed in Table 1, withanolides are predominant in 25 genera (including Acnistus, Datura, Deprea, Discopodium, Dunalia, Iochroma, Jaborosa, Lycium, Nicandra, Physalis, Solanum, Trechonaetes, Tubocapsicum, Vassobia, Withania, and Witheringia) of the Solanaceae family [2][3][4][5][6][7][10][11][12]. Not limited to the Solanaceae, withanolides have also been isolated from a smaller number of species in the Dioscoreaceae [13], Fabaceae [7], Lamiaceae [2], Myrtaceae [14], Taccaceae [2], and from two genera in the marine Alcyoniidae [15,16].…”

Section: Introductionmentioning

confidence: 99%

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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“…Over the last 46 years, approximately 750 withanolides, exhibiting more than 22 carbon skeletons (Figure 2), have been reported from various plant sources. As listed in Table 1, withanolides are predominant in 25 genera (including Acnistus , Datura , Deprea , Discopodium , Dunalia , Iochroma, Jaborosa , Lycium , Nicandra , Physalis , Solanum , Trechonaetes , Tubocapsicum , Vassobia , Withania and Witheringia ) of the Solanaceae family [2—7, 10—12]. Not limited to the Solanaceae, withanolides have also been isolated from a smaller number of species in the Dioscoreaceae [13], Fabaceae [7], Lamiaceae [2], Myrtaceae [14], Taccaceae [2], and from two genera in the marine Alcyoniidae [15, 16].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative withanolides from the Solanaceae: A structure–activity study

Zhang

Samadi

Cohen

et al. 2012

Pure and Applied Chemistry

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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, andWithania 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 IC50values 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 ∆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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New withanolides from Mandragora officinarum: First report of withanolides from the Genus Mandragora

Cited by 16 publications

References 11 publications

Third DWF1 paralog in Solanaceae, sterol Δ ²⁴ -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Third DWF1 paralog in Solanaceae, sterol Δ ²⁴ -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Antiproliferative withanolides from the solanaceae: A structure-activity study

Antiproliferative withanolides from the Solanaceae: A structure–activity study

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New withanolides from Mandragora officinarum: First report of withanolides from the Genus Mandragora

Cited by 16 publications

References 11 publications

Third DWF1 paralog in Solanaceae, sterol Δ 24 -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Third DWF1 paralog in Solanaceae, sterol Δ 24 -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Antiproliferative withanolides from the solanaceae: A structure-activity study

Antiproliferative withanolides from the Solanaceae: A structure–activity study

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Third DWF1 paralog in Solanaceae, sterol Δ ²⁴ -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Third DWF1 paralog in Solanaceae, sterol Δ ²⁴ -isomerase, branches withanolide biosynthesis from the general phytosterol pathway