New cytotoxic withanolides from Physalis peruviana

Lan, Yu; Chang, Fang Rong; Pan, Mei Jung; Wu, Chin Chung; Wu, Shu Jing; Chen, Su Li; Wang, Shyh Shyan; Wu, Ming; Wu, Yang Chang

doi:10.1016/j.foodchem.2009.02.061

Cited by 92 publications

(72 citation statements)

References 25 publications

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“…Direct comparison revealed that opening of the 5β,6β-epoxy-group of withaferin A 1 to furnish the corresponding 5β,6α-diol 29 or 6α-chloro-5β-ol 30 resulted in loss of activity. These findings confirm that the 5β,6β-epoxy-group in ring B is essential for the observed cytotoxic activity, in agreement with results previously reported in the literature for compounds with similar structural features [25][26][27].…”

Section: Resultssupporting

confidence: 93%

“…On the other hand, esterification of the hydroxyl groups at C-4, C-19, and C-27 increased cytotoxicity when comparing withaferin A 1 with withaferin A 4,27-diacetate 2; withalongolide A 6 with withalongolide A 4,27-diacetate 7 and withalongolide A 4,19,27-triacetate 8; withalongolide B 9 with withalongolide B 4-acetate 10 and withalon-golide B 4,19-diacetate 11 ( Table 2). These results are in agreement with previously reported SARs [24][25][26][27]31]. It should be noted that the cytotoxic activity of withalongolide B 9 is comparable to that of withaferin A 1, while the triacetate derivative 8 and diacetate derivative 11 are more potent than withaferin A 1 by exhibiting submicromolar activity with IC 50 values in the range of 0.067-0.91 μM against all the cell lines tested.…”

Section: Resultssupporting

confidence: 92%

“…In addition, it has been reported that when the 5β,6β-epoxy moiety in ring B is replaced by 5α-chloro-6β-hydroxy-functionality, the cytotoxicity of the two withanolides was comparable and in most cases the activity increased in the presence of the latter functional array. Several pairs of withanolides were compared for their activities, and similar results could be found in the literature: withanolide C 61 and withanolide E 36 [26]; physagulin I 62 and physagulin H 42 [38]; physagulin B 63 and 4-deoxy-withangulatin A 44 [38]; physagulin B 63 and withangulatin 45 [40]; and trechonolide A 64 and jaborosalactone 42 65 [27].…”

Section: -Oh Groupsupporting

confidence: 55%

“…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]. Withaferin A 1 (Fig.…”

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: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 92%

Section: -Oh Groupsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antiproliferative withanolides from the solanaceae: A structure-activity study

Zhang¹,

Samadi²,

Gallagher³

et al. 2012

Planta Med

View full text Add to dashboard Cite

show abstract

“…The effects of salpichrolides C (342) and G (340) differed from one insect species to the other, thus both compounds produced development delays only at high concentrations (2,000 ppm) in M. domestica and C. capitata, but salpichrolide G was almost as effective as salpichrolide A in T. castaneum. Regarding toxicity, the three salpichrolides produced significant mortality for M. domestica larvae (EC 50 200-300 ppm), but only salpichrolides A and G had this effect on C. capitata. The authors proposed that differences could be related to different detoxifying mechanisms.…”

Section: Antifeedant and Growth Inhibitionmentioning

confidence: 98%