The structure of amoorastatone and the cytotoxic limonoid 12-hydroxyamoorastatin

Polonsky, Judith; Varon, Zoīa; Marazano, Christian; Arnoux, B.; Pettit, George R.; Schmid, Jean; Ochi, Masamitsu; Kotsuki, Hiyoshizo

doi:10.1007/bf01949897

Cited by 49 publications

(24 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The known compounds were identified as the protolimonoids meliasenin B ( 3 ), cinamodiol ( 4 ), methyl kulonate ( 5 ), and 16‐hydroxybutyrospermol ( 6 ), trichilin‐class limonoids toosendanin ( 7 ), isotoosendanin ( 8 ), amoorastatone ( 9 ), 12‐hydroxyamoorastatone ( 10 ), mesendanin H ( 11 ), and meliatoosenin E ( 12 ), and salannin‐class (C‐seco) limonoids salannal ( 13 ), 3‐ O ‐acetylohchinolal ( 14 ), salannin ( 15 ), and ohchinal ( 16 ) by comparing their spectroscopic data with those found in the literatures.…”

Section: Resultsmentioning

confidence: 99%

Characterization of Limonoids Isolated from the Fruits of Melia toosendan and Their Antifeedant Activity against Pieris rapae

Wang

Dong

et al. 2020

Chemistry & Biodiversity

View full text Add to dashboard Cite

We thank Prof. Dr. Jia-Mei Li in Henan Agricultural University for the identification of the plant material.The fruits of Melia toosendan SIEB. et ZUCC. (Meliaceae) are a source of bioactive limonoids that can be used as effective pesticides. In this study, two novel limonoids, 6-acetylsendanal and 6-ketocinamodiol, were isolated together with fourteen known compounds, namely four protolimonoids, six trichilin-class limonoids, and four Cseco limonoids. The structures of the new compounds were determined by extensive spectroscopic analyses (HR-ESI-MS, UV, IR, 1D and 2D NMR). The bioassay results revealed that eleven of the extracted limonoids exhibited interesting antifeedant activities against the larvae of Pieris rapae with AFC 50 values in the range of 0.11 -1.79 mM. Particularly, mesendanin H, with an AFC 50 value of 0.11 mM, exhibited a higher activity than the positive control toosendanin. Information on new bioactive limonoids may provide further insight into M. toosendan as a source of bioactive components.

show abstract

Section: Resultsmentioning

confidence: 99%

Characterization of Limonoids Isolated from the Fruits of Melia toosendan and Their Antifeedant Activity against Pieris rapae

Wang

Dong

et al. 2020

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…In previous research conducted by our group, the fractionation of a kernel extract obtained from Melia azedarach L. led to the isolation of meliartenin, an antifeedant limonoid, which exists as a mixture with its tautomeric isomer 12hydroxyamoorastatin (Carpinella et al, 2002). The cytotoxicity of 12hydroxyamoorastatin, in terms of its half-inhibitory concentration (IC 50 ) against a few tumor cell lines, has been previously reported (Ahn et al, 1993;Itokawa et al, 1995;Polonsky et al, 1979). However, despite its potential as an antitumor drug, the mechanistic details involved in its biological effect together with meliartenin, have not yet been explored.…”

Section: Introductionmentioning

confidence: 99%

P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach

Joray

Villafañez

González

et al. 2017

Food and Chemical Toxicology

View full text Add to dashboard Cite

This work examines the antitumor activity of an isomeric mixture (1), composed of the limonoids meliartenin and its interchangeable isomer 12-hydroxyamoorastatin. The results obtained showed that 1 displayed outstanding cytotoxic activity against CCRF-CEM, K562, A549 and HCT116 cells, with a highly selective effect on the latter, with an IC value of 0.2 μM. Based on this finding, HCT116 cells were selected to study the mechanism of action of 1. Cell cycle analysis revealed that 1 induced sustained arrest in the S-phase, which was followed by the triggering of apoptotic cell death and reduced clonogenic capacity. This cytotoxicity was seen to be preceded by the upregulation of the tumor suppressor p53 and its target effector p21. In addition, it was found that p53 expression was required for efficient cell death induction, and thus that the toxicity of 1 relies mainly on p53-dependent mechanisms. Taken together, these findings position 1 as a potent antitumor agent, with potential for the development of novel chemotherapeutic drugs based on the induction of S-phase arrest.

show abstract

“…The ethyl acetate fraction of rohituka has been found to protect against the radiation-induced chromosome damage [21]. Certain alkaloids like, amoorastatin and 12-hydroxyamoorastatin, present in the stem bark extract of rohituka have been reported to exhibit cytotoxic and growth inhibitory activities in murine P388 lymphocytic leukaemia cells [22]. Rohituka has been reported to contain certain alkaloids and limonoids [23,24].…”

Section: Introductionmentioning

confidence: 99%

Determination of Antineoplastic Activity of Rohituka, Aphanamixis Polystachya (Wall) RN Parker in Hela Cells: Correlation with Clonogenicity and DNA Damage

Jagetia

Venkatesha

2016

IJCAM

View full text Add to dashboard Cite

The antineoplastic activity of chloroform stem bark extract of rohituka, Aphanamixis polystachya (APE) used traditionally to treat spleen and liver tumors was evaluated in cultured HeLa cells by clonogenic and micronucleus assays. Treatment of HeLa cells with 0, 5, 10, 25, 50, 75 or 100µg/ml APE for different times caused a concentration-dependent reduction in the cell survival up to 6 h post-treatment (p<0.005) followed by a non-significant decline in the cells treated with APE for 24 h. Therefore, 6h treatment time was considered as an optimum time for APE exposure and further studies were carried out using this treatment time. Exposure of HeLa cells to different concentrations of APE resulted in a concentration-dependent decline in the cell viability and 100µg/ ml APE resulted in 72% cell death when compared with the non-drug treated control group. These results were further confirmed by clonogenic assay where, APE treatment caused a concentration-dependent decline in the clonogenicity of HeLa cells, and the surviving fraction of cells was reduced to 0.22 after treatment with 100µg/ml APE, the highest concentration screened. The inhibitory concentration (IC50) of APE was found to be 25µg/ml. The APE-induced DNA damage was estimated by micronucleus assay, where the treatment of HeLa cells with various concentrations of APE resulted in a concentration-dependent rise in the frequency of micronuclei in binucleate HeLa cells (MNBNCs) at 20, 30, and 40 h post-treatment. This increase in MNBNCs was significantly higher than the baseline frequency of MNBNCs. APE treatment also increased the frequency of HeLa cells bearing more than one micronucleus (MN) indicating higher degree of DNA damage. The frequency of MNBNC increased with scoring time and a maximum elevation in the MNBNC frequency was observed at 30 h posttreatment. The MNBNC induction and clonogenicity of HeLa cells was inversely related indicating that increased MNBNC formation resulted in a corresponding reduction in the cell survival. The cell proliferation indices (PI) declined with increasing concentration of APE that increased with screening time. Our study demonstrates that APE is able to kill HeLa cells effectively and this cell killing effect of APE may be due its ability to induce DNA damage.

show abstract

The structure of amoorastatone and the cytotoxic limonoid 12-hydroxyamoorastatin

Cited by 49 publications

References 11 publications

Characterization of Limonoids Isolated from the Fruits of Melia toosendan and Their Antifeedant Activity against Pieris rapae

Characterization of Limonoids Isolated from the Fruits of Melia toosendan and Their Antifeedant Activity against Pieris rapae

P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach

Determination of Antineoplastic Activity of Rohituka, Aphanamixis Polystachya (Wall) RN Parker in Hela Cells: Correlation with Clonogenicity and DNA Damage

Contact Info

Product

Resources

About