Cytotoxicity of withanolides isolated from Acnistus arborescens

Cordero, Claudia P.; Morantes, Sandra Johanna; Páez, Alexandra; Rincón, Javier; Aristizábal, Fabio

doi:10.1016/j.fitote.2009.05.011

Cited by 46 publications

(40 citation statements)

References 32 publications

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“…From the biogenetic origin, it is likely that type I compounds are precursors to the more advanced structural types II−XXII. Type I withanolides that display the most promising antiproliferative characteristics also contain Δ 2 -1-oxo-functionality in ring A, a 5β,6β-epoxy-group in ring B, and a nine-carbon side chain incorporating the δ-lactone functionality found in withaferin A 1 [17], withacnistin 59 [18,19], withanolide D 48 [20][21][22][23], withanolide E 36 [8,[24][25][26][27], and 4β-hydroxywithanolide E 37 (Fig. 4) [8,[24][25][26][27].…”

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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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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“…The high activity observed for compound 3 was likely due to its good aqueous solubility and its spontaneous conversion in the cell culture media to the corresponding withaferin A which contains a 2,3-unsaturated ketone moiety (Xu et al, 2009). Interestingly, in contrast to previous observations (Cordero et al, 2009;Machin et al, 2010), the replacement of the 5,6-epoxy functionality with a 5,6-unsaturated group (compound 1) led to an increase in activity.…”

Section: Cytotoxic Activitymentioning

confidence: 77%

Cytotoxic withanolides from the leaves of MoroccanWithania frutescens

Bouzidi

Mahiou-Leddet

Bun

et al. 2013

Pharmaceutical Biology

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Context: Withania species are a rich source of interesting phytochemical substances (withanolides) which have shown several biological properties. Objective: To investigate the cytotoxic potential of Withania frutescens (L.) Pauquy (Solanaceae) leaf extracts and isolated active compounds against cultured tumor cell lines. Materials and methods: The crude methanol extract of W. frutescens leaves was partitioned with dichloromethane, ethyl acetate and n-butanol. MeOH extract and its fractions were tested for their cytotoxic activity against cancer cell lines (HepG2 and HT29) using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Bioassay-guided fractionation was performed for the active CH 2 Cl 2 fraction employing column chromatography and preparative high-performance liquid chromatography. Structural elucidation of the isolated active compounds was carried out mainly by 1D and 2D NMR and mass spectrometry. The compounds were then tested for their cytotoxic activity. Results: The CH 2 Cl 2 fraction was the most active against HT29 cell line. The fractionation procedure resulted in the isolation of 4b,17a,27-trihydroxy-1-oxo-22-R-witha-2,5,24-trienolide (1), 5b,6b-epoxy-4b,17a,27-trihydroxy-1-oxowitha-2,24-dienolide (2) and 2,3-dihydroxywithaferin A-3b-O-sulfate (3). The latter exhibited the strongest cytotoxic activity against HT29 cancer cell lines (IC 50 of 1.78 AE 0.09 mM) which was comparable to that of 5-fluorouracil (5-FU) used as the positive antimitotic control. Discussion and conclusion: Compounds 2 and 3 were isolated from W. frutescens for the first time. Data obtained suggest that the sulfated steroidal lactone (3) can be considered as a compound with potential application in the new anticancer drugs development field.

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“…The 1 H NMR, 13 C NMR, and HSQC spectra of 1 revealed the presence of six methyls [δ H 0.95 (3H, s), δ C 16.4; δ H 1.29 (3H, s), δ C 20.8; δ H 1.41 (3H, s), δ C 17.9; δ H 1.88 (3H, s), δ C 12.7; δ H 1.95 (3H, s), δ C 20.9; δ H 1.99 (3H, s), δ C 21.2], four methylenes [δ H 2.05 (1H, m), 1.45 (1H, m), δ C 30.0; δ H 1.89 (1H, m), 1.42 (1H, m), δ C 22.1; δ H 1.94 (1H, m), 1.43 (1H, m), δ C 40.2; δ H 2.51 (1H, m), 2.23 (1H, dd, J = 17.0, 3.1 Hz), δ C 31.1], 11 methines [including two olefinic at δ H 6.19 (1H, d, J = 10.0 Hz), δ C 132.1; δ H 6.93 (1H, ddd, J = 10.0, 5.8 Hz), δ C 142.2 and five oxygenated at δ H 3.21 (1H, br s), δ C 62.8; δ H 3.76 (1H, dd, J = 5.7, 1.9 Hz), δ C 69. 8;δ H 4.13 (1H,dd,J = 13.3,3.5 Hz), δ C 80. 4;δ H 5.16 (1H,dd,J = 11.4,7.8 Hz), δ C 71.6; δ H 5.60 (1H, t, J = 7.6 Hz), δ C 71.7], and nine quaternary carbons [including three carbonyl (δ C 202.…”

Section: ■ Results and Discussionmentioning

confidence: 99%