Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (II): apoptosis of antiproliferactive principle (24,25-dihydrowithanolide D) against ATL cell lines and structure–activity relationships with withanolides isolated from solanaceous plants

Nakano, Daisuke; Ishitsuka, Kenji; Katsuya, Hiroo; Kunami, Naoko; Nogami, Rumiko; Yoshimura, Yuka; Matsuda, Michika; Kamikawa, Mio; Tsuchihashi, Ryota; Okawa, Masafumi; Ikeda, Tsuyoshi; Nohara, Toshihiro; Tamura, Kazuo; Kinjo, Junei

doi:10.1007/s11418-012-0700-9

Cited by 11 publications

(10 citation statements)

References 18 publications

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“…The aliphatic ether side chain at C-5 also seems to increase the activity because as the side chain is lengthened, the activity increases. Because the EC 50 value for 4β-hydroxywithanolide E ( 93 ) was in the nanomolar range against both MT-1 and MT-2 cells, 31 other withanolides were also evaluated [ 33 ]. Except for compound 98 , none of the glycosides showed any activity against the ATL cell lines.…”

Section: Active Principlesmentioning

confidence: 99%

“…In contrast, the cytotoxic effect (860 nM) of 101 toward normal cells was observed at a concentration about 100 times higher than those observed for the ATL cell lines. Furthermore, compound 101 was confirmed to induce dose-dependent apoptosis against MT-1, MT-2, and fresh ATL cells [ 33 ]. Therefore, 24, 25-dihydrowithanolide D ( 101 ) may be a promising chemotherapeutic candidate.…”

Section: Active Principlesmentioning

confidence: 99%

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Screening of promising chemotherapeutic candidates from plants extracts

et al. 2016

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Over the course of our studies investigating anti-proliferative properties of compounds originating from plants against human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), murine melanoma (B16F10), and two human T cell lymphotropic virus type 1 (HTLV-1)-infected T-cell lines (MT-1 and MT-2), we have screened 582 extracted samples obtained from a variety of parts from 370 plants. A few extracts showed anti-proliferative activity against all cell lines, but upon further investigation, toxicity toward selected cell lines was recognized. After activity-guided fractionation, isolation of the active principles was achieved. Structure–activity relationship studies identified the components and functionalities responsible for the specific selectivity against each cancer cell line. The effect of polyacetylenes against MK-1 cells was more potent than against HeLa and B16F10 cells. The compound having a 3,4-dihydroxyphenethyl group also showed an anti-proliferative effect against B16F10 cells. Some 6-methoxyflavone derivatives and 8-hydroxy furanocoumarins were good inhibitors of HeLa cell growth. The 17 compounds whose EC50 values were less than 1 nM did not show specific cellular selectivity. Because the cytotoxic effect of 24, 25-dihydrowithanolide D toward control cells was observed at a concentration about 100 times higher than those for the cancer cell lines, withanolide was identified as the most promising chemotherapeutic candidate in our experiments.

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Section: Active Principlesmentioning

confidence: 99%

Section: Active Principlesmentioning

confidence: 99%

Screening of promising chemotherapeutic candidates from plants extracts

et al. 2016

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“…Dihydrowithanolide D ( 14 ) was isolated from the aerial parts and leaves of W . somnifera and possesses potent cell differentiation inducing activity against M1 cells and antiproliferactive activity against ATL cell lines . 23,24‐Dihydrowithferin A 15 ( Fig .…”

Section: Resultsmentioning

confidence: 99%

Metabolite Profiling in Withania somnifera Roots Hydroalcoholic Extract Using LC/MS, GC/MS and NMR Spectroscopy

Trivedi¹,

Panda²,

Sethi³

et al. 2017

Chemistry & Biodiversity

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Ashwagandha (Withania somnifera) is a very well-known herbal medicine and it was well studied for its active metabolites throughout the World. Although, nearly 40 withanolides were isolated from W. somnifera root extract, still there is remaining unidentified metabolites due to very low abundance and geographical variation. Advanced separation technology with online identification by mass and nuclear magnetic resonance (NMR) are nowadays used to find out the new compounds in the crude herbal extract. This article described the metabolite profiling of ashwagandha root hydroalcoholic extract using ultra-performance liquid chromatography coupled with a positive ion electrospray ionization tandem mass spectrometry through gas chromatography mass spectrometry (GC/MS) and NMR spectroscopy. A total of 43 possible withanolides was identified and proposed their structures based on the mass of molecular and fragment ions. GC/MS and NMR analysis indicated the presence of several known withanolides including withaferin A, withanolide D, withanoside IV or VI, withanolide sulfoxide, etc. To the best of our knowledge, dihydrowithanolide D at m/z 473 (t 7.86 min) and ixocarpalactone A at m/z 505 (t 8.43 min) were first time identified in the ashwagandha root hydroalcoholic extract. The current study that described the identification of withanolides with summarized literature review might be helpful for designing the experiment to identify of the new chemical constituents in Withania species.

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“…In terms of the structureactivity relationship, it was previously proposed that the presence of an a,b-unsaturated ketone and a 5b,6b-epoxy system is necessary for the antiproliferative activity of withanolides (Zhang et al, 2012). In addition, it was reported that the presence of a 4b-hydroxy group also leads to enhanced antiproliferative activity (Nakano et al, 2012). 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).…”

Section: Cytotoxic Activitymentioning

confidence: 99%

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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Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (II): apoptosis of antiproliferactive principle (24,25-dihydrowithanolide D) against ATL cell lines and structure–activity relationships with withanolides isolated from solanaceous plants

Cited by 11 publications

References 18 publications

Screening of promising chemotherapeutic candidates from plants extracts

Screening of promising chemotherapeutic candidates from plants extracts

Metabolite Profiling in Withania somnifera Roots Hydroalcoholic Extract Using LC/MS, GC/MS and NMR Spectroscopy

Cytotoxic withanolides from the leaves of MoroccanWithania frutescens

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