Biochemical and biophysical properties of a novel homoisoflavonoid extracted from Scilla persica HAUSSKN

doi:10.1016/j.bioorg.2014.08.001

Bioorganic Chemistry

Volume 57, December 2014, Pages 51-56

https://doi.org/10.1016/j.bioorg.2014.08.001 Get rights and content

Highlights

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Structure elucidation of a novel Homoisoflavonoid that was identified as Scillapersicone.
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The structure of Scillapersicone was established by single crystal X-ray analysis.
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The low energy gap of Scillapersicone can caused cytotoxicity on cancerous cell lines.

Abstract

In this study isolation and structural elucidation of a homoisoflavonoid, 3-(3′,4′-dihydroxybenzyl)-8-hydroxy-5,7-dimethoxychroman-4-one (Scillapersicone 1), is reported from Scilla persica HAUSSKN. The structure was solved by a single crystal X-ray analysis. The unit cell parameters are a = 11.7676 (2) Å, b = 20.1174 (4) Å, c = 7.8645 (9) Å, β = 93.544 (2)°, V = 1858.23 (7) Å³, monoclinic space group P2₁/c and four symmetry equivalent molecules in an unit cell. The structure was consistent with the UV, IR, 1D and 2D NMR, HRFAB-MS data. The optimized molecular geometry agrees closely that obtained from the single crystal X-ray crystallography. Furthermore, cytotoxicity of this compound was evaluated by MTT assay on AGS and WEHI-164 cancerous cell lines.

Graphical abstract

Introduction

Scilla persica HAUSSKN is a perennial herb belonging to the Liliaceae family [1]. It is known as a foodstuff and important plant in traditional medicine for promoting blood circulation, reducing inflammation, as an analgesic [2], and antibacterial agent [3]. Previous studies on Scilla species revealed triterpenoid [4], stilbenoids [5] and cardiac glycosides [6] as well as homoisoflavanones [7], [8], [9], [10], [11], which showed antibacterial and anti-angiogenic activities, and inhibited in vitro the growth and sporogenesis of several microorganisms [7], [8], [11], [12]. Homoisoflavonoids purely represent a modification of the flavonoid-type skeleton. Feeding experiments showed that the biosynthesis of 3-benzylchroman-4-ones consists in modification of the C₆ single bond C₃C₆ chalcone/flavonoid pathway by insertion of an extra carbon atom [13]. These compounds were mainly discovered from plants belonging to the Liliaceae family and a few other plant species [14], and they were recorded to be responsible for biomedical activities of these plants, such as antioxidant activity [15], [16], [17], cytotoxic activity [18], [19], [20], inhibition of platelet aggregation [21], cough relief [22], hyperglycemia [23], anti-fungal [12], anti-inflammatory, anti-allergic, antihistaminic and angioprotective activities. They have been also detected as potent phosphodiesterase inhibitors [11], [24], [25]. In this paper, we report the isolation, structural elucidation, and physical chemistry of a novel homoisoflavonoid, Scillapersicone 1, which was obtained from fresh bulbs of S. persica (Fig. 1, Fig. 2). Moreover, the cytotoxicity of this compound on AGS and WEHI-164 cancerous cell lines is reported.

Section snippets

Plant material

Fresh bulbs of Scilla persica HAUSSKN were collected in the village of Valliv from Sardasht, West Azerbaijan Province, Iran, in March 2012 at an altitude of 1700–1800 m. The plant was identified by Afsaneh Kolbadi (Agriculture and Natural Resources Research Center, Sari, Iran), and a voucher specimen (No. 6334) was deposited in the Herbarium of the same institute.

Instruments and materials

UV spectra were obtained in MeOH using a Shimadzu UV-PC 2501 spectrometer. IR spectra were recorded on a Perkin-Elmer FT-IR

Structure elucidation of Scillapersicone (1)

Scillapersicone (1) was obtained as yellowish needles with molecular formula of C₁₈H₁₈O₇, as established by HRFAB-MS (m/z 347.1145 [M+H]⁺; calcd. 347.1131). The IR absorptions at 3412 cm⁻¹ and 1664 cm⁻¹ implied the existence of hydroxyl and carbonyl groups, respectively. The ¹H and ¹³C NMR chemical shifts together with the HSQC and HMBC results are summarized in Table 2. The ¹H NMR spectrum together with the HMBC spectrum showed the presence of a singlet aromatic proton signal at δ_H 6.39 (δ_C

Concluding remarks

A homoisoflavonoid, named Scillapersicone (1), was isolated from the medicinal plant S. persica HAUSSKN. The structure was established by spectroscopic methods and X-ray crystallographic analysis. The molecular geometry was also investigated with theoretical calculations using the B3LYP and HF methods with the 6-311++G** level of theory, yielding results close to the experimental data obtained from X-ray crystallography. Many homoisoflavonoids have been isolated from Liliaceae family as well as

Acknowledgments

The authors wish to thank Mr. Abbas Biglari (Zanjan Institute of Chemistry for NMR spectroscopic measurements, and Dr. Ahmad Reza Gohari and other MPRC colleagues (Medicinal Plants Research Center, Tehran University of Medical Sciences) for their support in isolation and purification process. The authors are also grateful to Golestan University and Tabriz University Research Councils for partial support of this work and the project (14-03276S) of the Grant Agency of the Czech Republic.

References (34)

V. Bangani et al.
Phytochemistry
(1999)
A. Silayo et al.
Phytochemistry
(1999)
J. Mutanyatta et al.
Phytochemistry
(2003)
K.V.N.S. Srinivas et al.
Phytochemistry
(2003)
P.M. Dewick
Phytochemistry
(1975)
E. Sievanen et al.
J. Mol. Struct.
(2010)
V. Siddaiah et al.
Bioorg. Med. Chem.
(2006)
Y.F. Zhou et al.
Chin. J. Nat. Med.
(2008)
A. Nguyen et al.
Phytochemistry
(2006)
J. Yan et al.
Phytochemistry
(2012)

C.T. Yen et al.

Bioorg. Med. Chem. Lett.

(2010)

S.B. Choi et al.

Life Sci.

(2004)

E. Babaei et al.

Int. Immunopharmacol.

(2012)

M.T. Baei et al.

Comput. Theor. Chem.

(2011)

T.C. Ramalho et al.

Biophys. Chem.

(2004)

A. Soltani et al.

Appl. Surf. Sci.

(2012)

V. Mozzafarian

Dictionary of the Names of Iranian Plants

(1997)

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Homo-isoflavonoids are naturally present in the form of a C6–C3–C6 chalcone backbone. They activate PI3K/Akt signaling and promote glucose uptake via the translocation of glucose transporter 4 to the plasma membrane in adipocytes (Ghoran. et al., 2014; Choi et al., 2004). These effects are due to hydroxyl or methoxy groups in the homo-isoflavonoid structure, with more of these groups indicating greater effects (Zhang et al., 2010).
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Homoisoflavonoids from the bulbs of Bellevalia longipes and an assessment of their potential cytotoxic activity
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Biochemical and biophysical properties of a novel homoisoflavonoid extracted from Scilla persica HAUSSKN

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Plant material

Instruments and materials

Structure elucidation of Scillapersicone (1)

Concluding remarks

Acknowledgments

Phytochemistry

Phytochemistry

Phytochemistry

Phytochemistry

Phytochemistry

J. Mol. Struct.

Bioorg. Med. Chem.

Chin. J. Nat. Med.

Phytochemistry

Phytochemistry

Bioorg. Med. Chem. Lett.

Life Sci.

Int. Immunopharmacol.

Comput. Theor. Chem.

Biophys. Chem.

Appl. Surf. Sci.

Dictionary of the Names of Iranian Plants