Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles from Physalis pruinosa and structure–activity relationships with withanolides

Nakano, Daisuke; Ishitsuka, Kenji; Hatsuse, Takahiro; Tsuchihashi, Ryota; Okawa, Masafumi; Okabe, Hikaru; Tamura, Kazuo; Kinjo, Junei

doi:10.1007/s11418-011-0543-9

Cited by 18 publications

(9 citation statements)

References 16 publications

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“…After activity-guided fractionation against MT-1 and MT-2 cells, five active withanolides ( 93 – 97 ) were isolated from the aerial parts of Physalis pruinosa (Solanaceae) [ 32 ]. Structure–activity relationships suggested that the presence of a 5β, 6β epoxy group in the B-ring and a 4β-hydroxy group in the A-ring were important for the observed activities.…”

Section: Active Principlesmentioning

confidence: 99%

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%

Screening of promising chemotherapeutic candidates from plants extracts

et al. 2016

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“…Resazurin reduction assay is well known and has been employed in some studies to screen compounds for ATL treatment due its reliability to test cell proliferation and/or viability and evaluate anti-proliferative effect on MT-1 and MT-2 cell lines. 27 For instance, a range of plant extracts have been tested by this method to isolate components with potent inhibitory activity for further tests, 28,29 and YM155, an antitumor imidazolium compound and potent inhibitor of Survivin, was tested on a variety of human cancer cell lines, including T-acute lymphoblastic leukemia (T-ALL). 30 The initial screening on HTLV-1-infected cell line (MT-2) led us to select eight compounds (02, 05, 06, 13, 15, 21, 22 and 25) (Figure 2) for further studies as they significantly reduced the metabolic activity of the cells (≥ 70%) in a similar manner to the positive control (ETO).…”

Section: Discussionmentioning

confidence: 99%

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Santos

Pilger

Vandermeulen

et al. 2020

Bioorganic & Medicinal Chemistry

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Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that infects approximately 10-20 million people worldwide and causes an aggressive neoplasia (adult T-cell leukemia/lymphoma -ATL). Therapeutic approaches for the treatment of ATL have variable effectiveness and poor prognosis, thus requiring strategies to identify novel compounds with activity on infected cells. In this sense, we initially screened a small series of 25 1,2,3-triazole derivatives to discover cell proliferation inhibitors and apoptosis inducers in HTLV-1-infected T-cell line (MT-2) for further assessment of their effect on viral tax activity through inducible-tax reporter cell line (Jurkat LTR-GFP).Eight promising compounds (02, 05, 06, 13, 15, 21, 22 and 25) with activity ≥ 70% were initially selected, based on a suitable cell-based assay using resazurin reduction method, and evaluated towards cell cycle, apoptosis and Tax/GFP expression analyses through flow cytometry. Compound 02 induced S phase cell cycle arrest and compounds 05, 06, 22 and 25 promoted apoptosis. Remarkably, compounds 22 and 25 were also able to reduce GFP expression in an inducible-tax reporter cell, which suggests an effect on Tax viral protein. More importantly, compounds 02, 22 and 25 were not cytotoxic in human hepatoma cell line (Huh-7). Therefore, the discovery of 3 active and non-cytotoxic compounds against HTLV-1-infected cells can potentially contribute, as an initial promising strategy, to the development process of new drugs against ATL.

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“…Secondary metabolite production in a host plant can also be triggered by the existence of a parasite, as discussed in a study on Tapirira guianensis infested by Phoradendron perrottetii, in which infested branches produced more tannin compare to non-infested branches, with infestation inducing a systemic response [48]. Against T-cell leukemia [197], antimicrobial [198] 111…”

Section: Epiphytic Plant-host Interactions On Secondary Metabolite Tamentioning

confidence: 99%

Vascular Epiphytic Medicinal Plants as Sources of Therapeutic Agents: Their Ethnopharmacological Uses, Chemical Composition, and Biological Activities

et al. 2020

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This is an extensive review on epiphytic plants that have been used traditionally as medicines. It provides information on 185 epiphytes and their traditional medicinal uses, regions where Indigenous people use the plants, parts of the plants used as medicines and their preparation, and their reported phytochemical properties and pharmacological properties aligned with their traditional uses. These epiphytic medicinal plants are able to produce a range of secondary metabolites, including alkaloids, and a total of 842 phytochemicals have been identified to date. As many as 71 epiphytic medicinal plants were studied for their biological activities, showing promising pharmacological activities, including as anti-inflammatory, antimicrobial, and anticancer agents. There are several species that were not investigated for their activities and are worthy of exploration. These epipythes have the potential to furnish drug lead compounds, especially for treating cancers, and thus warrant indepth investigations.

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Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles from Physalis pruinosa and structure–activity relationships with withanolides

Cited by 18 publications

References 16 publications

Screening of promising chemotherapeutic candidates from plants extracts

Screening of promising chemotherapeutic candidates from plants extracts

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Vascular Epiphytic Medicinal Plants as Sources of Therapeutic Agents: Their Ethnopharmacological Uses, Chemical Composition, and Biological Activities

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