Synthesis, Characterization, and Antioxidant Activities of Genistein, Biochanin A, and Their Analogues

Hamza Sherif, Salah; Gebreyohannes, BerihuTekluu

doi:https://doi.org/10.1155/2018/4032105

Journal of Chemistry

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Research Article | Open Access

Volume 2018 | Article ID 4032105 | https://doi.org/10.1155/2018/4032105

Synthesis, Characterization, and Antioxidant Activities of Genistein, Biochanin A, and Their Analogues

Salah Hamza Sherif¹and BerihuTekluu Gebreyohannes²

Academic Editor: Maria B. P. P. Oliveira

Received16 Jun 2017

Accepted28 Sept 2017

Published16 Jan 2018

Abstract

A series of naturally occurring genistein (3) and biochanin A (4) compounds and their analogues were synthesized from phloroglucinol. The structures of all the synthesized compounds were established by the combined use of , , IR spectral data, and mass spectrometry; their antioxidant activities were investigated. Most of the synthesized compounds show moderate-to-high activity; only two compounds exhibit no significant activity.

1. Introduction

Isoflavonoids (2) are one of the main subclasses of flavonoids (1) which contain C6-C3-C6 carbon skeleton based on 3-phenylchroman [1]. They are widely distributed in many plants [2, 3] and in various common foods which are particularly abundant in seeds and other parts of leguminous plants [4, 5]. Significant amounts of isoflavonoids were found in soybeans [6]. Epidemiological studies show that a high consumption of soybean derived foods correlates to a low incidence of hormone related diseases such as cancers, osteoporosis, and cardiovascular diseases [7]. Genistein (3) has been one of the most widely studied natural products and has exhibited a wide range of biological activities such as anticancer [8–11], antioxidant [12–16], and antimicrobial activities [17, 18]. Genistein can bind to both the Estrogen Receptor alpha (ERα) and the Estrogen Receptor beta (ERβ), although it has a higher affinity for the ERβ [19], and genistein is thought to exert its estrogenic effects through mechanisms similar to those of estradiol [20]. Biochanin A (4) is the 4′-O-methyl derivative of genistein and biochanin A is the predominant isoflavone found in alfalfa, Trifolium pratense, and Cicer arietinum [21] which has an inhibitory and apoptogenic effect on certain cancer cells such as pancreatic cancer and prostate cancer [22, 23].

The biological and biochemical activity, potential chemopreventive property, therapeutic properties, and genistein affinity towards a large variety of molecular targets attracted the interest of many researchers. The number of publications regarding the synthesis and biological evaluation of genistein and its derivatives has increased [24–27]. This paper presents the synthesis of genistein, biochanin A, and their synthetic analogues to investigate the antioxidant activities and the effect of various substituents on the activity of the molecule.

2. Results and Discussion

2.1. Antioxidant Activity

2.1.1. DPPH (1,1-Diphenyl-2-picrylhydrazyl) Radical Scavenging Activity

The DPPH radical scavenging activity of the synthesized compounds was carried out according to the method of [28]. The in vitro antioxidant activity of the final compounds 4(a–h) was evaluated by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging method. Ascorbic acid was used as the positive control. The DPPH radical scavenging activity was carried out at concentration of 100 μg/ml and the results were reported as average of three replicates. When DPPH reacts with an antioxidant compound, the decrease in absorbance observed because of the reaction between antioxidant molecules and radical progresses, which results in the scavenging of the radical by hydrogen donation. The hydrogen donating activity measured at 517 nm showed a significant relationship between concentration of compounds and percentage of inhibition. The structures of flavonoid, isoflavonoid, genistein, and biochanin A are shown in Figure 1.

The DPPH radical scavenging activity was expressed as % of inhibition and results are tabulated in Table 1. Among the target compounds 4(a–h), the compounds 4c (86.95) and 4b (84.89) exhibited maximum DPPH free radical scavenging activity followed by the compounds 4g (76.36), 4e (74.77), 4f (73.81), and 4h (65.56) which possess good radical scavenging activity when compared with the reference standard ascorbic acid (92.22). The compounds 4a and 4d exhibited no significant radical scavenging activity.

2.2. Procedure

The synthesized compounds were dissolved in DMSO at a concentration of 100 μg/ml. Ascorbic acid was used as a reference standard. 0.004% of DPPH was freshly prepared in methanol. 2 ml of DPPH was added to each test tube containing 100 μg/ml concentration of synthesized compounds 4(a–h) (1 ml) and of standard solution (1 ml). It was shaken vigorously. They were then allowed to stand for 30 min at room temperature in dark place. The control was carried without addition of DPPH and the synthesized compounds. DMSO was used for base line corrections and absorbance (OD) of sample was measured at 517 nm. The following formula was used to interpret the value of the sample:

2.3. Conclusions

The aim of the present work was to compare the radical scavenging activities of genistein and its analogues, which have various substituents at 4′ position of B-ring, and study the effect of these substituents on antioxidant activity.

The maximum inhibitory effect was exhibited by compound 4c, (5,7-dihydroxy-3-phenyl-4H-chromen-4-one) which lacks hydroxyl substituent on the B-ring, it has two hydroxyl groups on the A-ring (at C-5 and C-7), and the potent activity suggested that, in cases where the B-ring could not contribute to the inhibitory activity of the isoflavonoids, the hydroxyl group on the A-ring may become a major factor to show the activity. Compound 4h which has no hydroxyl group exhibited radical scavenging activity (). Compounds 4e, 4f, and 4g have comparable inhibitory activities. 4g (), 4e (), and 4f () exhibited moderate activity. The remaining two compounds, 4a and 4d, exhibited no significant radical scavenging activity.

3. Experimental Section

3.1. Materials and Methods

All chemicals and solvents were purchased from Sigma-Aldrich and used without further purification; the reaction process was monitored by TLC silica gel plates; the purification of the products was performed using column chromatography using silica gel (100–200 mesh). Melting points were measured in open capillary tubes and were uncorrected; infrared (IR) spectra were recorded using FT-IR Bruker Alpha spectrometer. NMR spectra were recorded on Bruker (400 MHz) spectrometer using TMS as the internal standard; mass spectra were recorded on an Agilent 110 Lc/MSD. Elemental analyses were performed on a Vario EL-III. The antioxidant activity of all the target compounds (4a–h) was investigated using DPPH (1,1-diphenyl-2-picrylhydrazyl) radical method.

3.2. Chemistry

The titled compounds (4a–h) described in this study were prepared as outlined in Scheme 1, according to the literature method [29]. The intermediate, substituted trihydroxybenzoin (3a, 3c–g) was prepared by acylation of phloroglucinol (1) with appropriately substituted phenyl acetonitrile (2a, 2c–g), catalyzed by HCl gas and anhydrous ZnCl₂ in dry ether. Cyclization of the intermediate (3a, 3c–g) with reagents of Et₂O·BF₃ and DMF/POCl₃ yielded the desired substituted isoflavonoids in good yield. There are several reagents for the demethylation of methyl aryl ethers; we used anhydrous AlCl₃ to synthesize genistein (4b) from biochanin A (4a) by demethylation of 4′-O-methyl of biochanin A. 4h was prepared by methylation of 4g using dimethyl sulphate in acetone in the presence of K₂CO₃.

3.3. Synthesis and Characterization

3.3.1. General Procedure for the Synthesis of Substituted 2′,4′,6′-Trihydroxydeoxybenzoins (3a, 3c–g)

To a solution of phloroglucinol (1) (5 g, 0.039 mol) and substituted phenyl acetonitrile (2a, 2c–g) (0.044 mol), in 100 ml dry ether in an ice-salt bath, 2 g anhydrous zinc chloride was added. A steady stream of dry hydrogen chloride gas was passed through the solution for 2 hrs of stirring continuously. The mixture was allowed to stand in refrigerator overnight and again dry hydrogen chloride gas was passed through the mixture for another 2 hours. After keeping the mixture in a refrigerator for three days, the ether was decanted and washed twice with ether; the solid obtained was hydrolyzed by refluxing with 100 ml 2% HCl water for 2 hours. After completion of the reaction the mixture was cooled, filtered, and dried to yield the target compounds.

1-(2,4,6-Trihydroxy)-2-(4-methoxyphenyl)ethanone (3a). Yield: 52%; Mp: 190–194°C; Anal. Calcd for C₁₅H₁₄O₅: C, 65.69; H, 5.15; O, 29.17; found: C, 65.62; H, 5.19; O, 29.19; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.94 (s, 2 H, -OH), 10.92 (s, 1H, -OH), 7.2 (d, J = 8.0 Hz, 2H, Ar-H), 6.8 (d, J = 8.0 Hz, 2H, Ar-H), 5.8 (s, 2H, Ar-H), 4.2 (s, 2H), 3.8 (s, 3H); NMR (DMSO-d₆, 100 MHz): δ 202.6, 164.7, 164.2, 157.8, 130.5, 127.7, 113.5, 103.6, 94.7, 54.9, 47.9; ESI-MS: 275 [M + H]⁺.

1-(2,4,6-Trihydroxyphenyl)-2-phenylethanone (3c). Yield: 47%, Mp: 158–161°C; Anal. Calcd for C₁₄H₁₂O₄: C, 68.85; H, 4.95; O, 26.20; found: C, 68.81; H, 4.98; O, 26.21; NMR (DMSO-d₆, 400 MHz,): δ12.22 (s, 2H, -OH), 10.39 (s, 1H, -OH), 7.31–7.19 (m, 5H, Ar-H), 5.83 (s, 2H, Ar-H), 4.35 (s, 2H); NMR (DMSO-d₆, 100 MHz): δ 202.2, 164.8, 164.2, 135.9, 129.6, 128.0, 126.1, 103.7, 94.7, 48.8; ESI-MS: 245 [M + H]⁺.

2-(4-Fluorophenyl)-1-(2,4,6-trihydroxyphenyl)ethanone (3d). Yield: 40%, Mp: 194–196°C; Anal. Calcd for C₁₄H₁₁FO₄: C, 64.12; H, 4.23; O, 24.40; found: C, 64.07; H, 4.25; O, 24.43; NMR (DMSO-d₆, 400 MHz,): δ12.19 (s, 2H, -OH), 10.39 (s, 1H, -OH), 7.27–7.23 (m, 2H, Ar-H), 7.11 (t, J = 9.2, 2H, Ar-H), 5.83 (s, 2H, Ar-H), 4.34 (s, 2H); ¹³CNMR (DMSO-d₆, 100 MHz): δ 202.0, 164.8, 164.2, 160.9 (d, = 241 Hz, 1C), 132.0 (d, = 3 Hz, 1C), 131.4 (d, = 8.0 Hz, 2C), 114.6 (d, = 21 Hz, 2C,) 103.6, 94.7, 48.0; ESI-MS: 263 [M + H]⁺.

1-(2,4,6-Trihydroxyphenyl)-2-(4-nitrophenyl)ethanone (3e). Yield: 58%, Mp: 222–224°C; Anal. Calcd for C₁₄H₁₁NO₆: C, 5.13; H, 3.83; N, 4.84; O, 33.19; found: C, 5.09; H, 3.84; N, 4.85; O, 33.21; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.21 (s, 2H, -OH), 10.92 (s, 1H, -OH), 8.22 (d, J = 8.8 Hz, 2H, Ar-H), 7.55 (d, J = 8.8 Hz, 2H, Ar-H), 5.89 (s, 2H, Ar-H), 4.57 (s, 2H,); ¹³C NMR (DMSO-d₆, 100 MHz):δ = 200.8, 165.1, 164.2, 146.2, 144.2, 131.1, 123.0, 103.7, 94.7, 48.83; ESI-MS: 290 [M + H]⁺.

1-(2,4,6-Trihydroxyphenyl)-2-p-tolylethanone (3f). Yield: 56%, Mp: 168–170°C; Anal. Calcd for C₁₅H₁₄O₄: C, 69.76; H, 5.46; O, 24.78; found: C, 69.72; H, 5.48; O, 24.80; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.22 (s, 2H, -OH), 10.38 (s, 1H, -OH), 7.09 (s, 4H, Ar-H), 5.81 (s, 2H, Ar-H), 4.28 (s, 2H,), 3.01 (s, 3H, CH₃); ¹³C NMR (DMSO-d₆, 100 MHz): δ202.5, 164.8, 164.2, 135.1, 132.8, 129.4, 128.6, 103.6, 94.6, 48.4, 20.6; ESI-MS: 259 [M + H]⁺.

2-(4-Bromophenyl)-1-(2,4,6-trihydroxyphenyl)ethanone (3g). Yield: 48%, Mp: 218–220°C; Anal. Calcd. for C₁₄H₁₁BrO₄: C, 52.04; H, 3.43; Br, 24.73; O, 19.80; found: C, 52.01; H, 3.44; O, 19.82; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.12 (s, 2H, -OH), 10.41 (s, 1H, -OH), 7.45 (d, J = 8.4 Hz, 2H, Ar-H), 7.18 (d, J = 8.8 Hz, 2H, Ar-H), 5.82 (s, 2H, Ar-H), 4.33 (s, 2H); ¹³C NMR (DMSO-d₆, 100 MHz): δ201.6, 164.9, 164.2, 135.3, 131.9, 130.8, 119.4, 103.6, 94.7, 48.31; ESI-MS: 323 [M + H]⁺.

3.3.2. General Procedure for the Cyclization of Substituted 2′,4′,6′-Trihydroxydeoxybenzoins (Synthesis of 4a, 4c–g)

With cooling and vigorous stirring (3 mL, 24 mmol), etherated boron trifluoride was added drop wise to 8 mmol of 3a, 3c–g in 3 ml of anhydrous DMF. The cooling was stopped and phosphorus oxychloride (0.9 ml, 9.6 mmol) was added dropwise; after mixing all the components the reaction mixture was stirred at 60–70°C for 2 h and then poured into acidified water; the precipitate was filtered off and purified by column chromatography using hexane and ethylacetate in the ratio of 8 : 2 as eluents.

5,7-Dihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one (4a). Yield: 61%, Mp: 212–214°C; Anal. Calcd. for C₁₆H₁₂O₅: C, 67.60; H, 4.25; O, 28.14; found: C, 67.57; H, 4.27; O, 28.15; ¹H NMR (DMSO-d₆, 400 MHz): δ12.94 (s, 1H, 5-OH), 10.92 (s, 1H, 7-OH), 8.38 (s, 1H, 2-H), 7.50 (d, J = 8.0 Hz, 2H, Ar-H), 7.0 (d, J = 8.0 Hz, 2H, Ar-H), 6.40 (1H, Ar-H), 5.77 (s, 1H, Ar-H), 3.79 (s, 3H); ¹³CNMR (DMSO-d₆, 100 MHz,): δ 180.0, 164.3, 161.9, 159.17, 157.5, 154.2, 130.1, 122.9, 121.9, 113.7, 104.4, 99.0, 93.6, 55.1; 24; ESI-MS: 285 [M + H]⁺; FT-IR (KBr, Cm⁻¹): 3312 (O-H), 3007, (C-H aromatic), 2950 (C-H aliphatic), 1642 (C=O);

5,7-Dihydroxy-3-phenyl-4H-chromen-4-one (4c). Yield: 76%, Mp: 194–196°C; Anal. Calcd. for C₁₅H₁₀O₄: C, 70.86; H, 3.96; O, 25.17; found: C, 70.82; H, 3.98; O, 25.19; ¹H NMR (DMSO-d₆, 400 MHz): δ10.81 (s, 1H, 7-OH), 8.39 (s, 1H, 2-H), 8.0 (d, J = 8.8 Hz, 2H, Ar-H), 7.58 (d, J = 8.0 Hz, 2H, Ar-H), 6.97 (d, J = 2.0 Hz, 1H, Ar-H), 6.88 (d, J = 2 Hz, 1H, Ar-H); ¹³CNMR (DMSO-d₆, 22.5 MHz): δ 174.3, 162.6, 157.4, 153.6, 153.5, 132.1, 128.8, 127.6, 123.58; ESI-MS: 255 [M + H]⁺; FT-IR (KBr, Cm⁻¹): 3198 (O-H), 3062, (C-H aromatic), 2925 (C-Haliphatic), 1626 (C=O).

3-(4-Fluorophenyl)-5,7-dihydroxy-4H-chromen-4-one (4d). Yield: 54%, Mp: 188–190°C; Anal. Calcd. for C₁₅H₉FO₄: C, 66.18; H, 3.33; F, 6.98; O, 23.51 found: C, 66.13; H, 3.34; O, 23.55; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.83 (s, 1H, 5-OH), 10.93 (s, 1H, 7-OH), 8.44 (s, 1H, 2-H), 7.63 (t, J = 8.8 Hz, 2H, Ar-H), 7.31 (t, J = 9.2 Hz, 2H, Ar-H), 6.42 (d, J = 1.6 Hz, 1H, Ar-H), 6.25 (d, J = 1.6 Hz, 1H, Ar-H); ¹³CNMR (DMSO-d₆, 22.5 MHz): δ 179.1, 164.6, 161.8, 156.2, 157.3, 147.01, 157.2, 156.2, 147.0, 137.8, 123.10; ESI-MS: 273 [M + H]⁺; FT-IR (KBr, Cm⁻¹): 3299 (O-H), 3077, (C-H aromatic), 2924 (C-H aliphatic), 1664 (C=O).

5,7-Dihydroxy-3-(4-nitrophenyl)-chroman-4-one (4e). Yield: 63%, Mp: 286–288°C; Anal. Calcd: for C₁₅H₉NO₆: C, 60.21; H, 3.03; N, 4.68; O, 32.08; found: C, 60.17; H, 3.05; N, 4.69; O, 32.09; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.70 (s, 1H, 5-OH), 11.01 (s, 1H, 7-OH), 8.63 (s, 1H, 2-H), 8.32 (d, J = 8.8 Hz, 2H, Ar-H), 7.91 (d, = 8.8 Hz, 2H, Ar-H) 6.46 (d, J = 1.6 Hz, 1H, Ar-H), 6.28 (d, J = 2 Hz, 1H, Ar-H); ¹³C NMR (DMSO-d₆, 22.5 MHz): δ 179.1, 164.6, 161.9, 157.4, 156.1, 146.8, 137.9, 123.15, 120.3, 104.3, 99.2; ESI-MS: 300 [M + H]⁺.; FT-IR (KBr, Cm⁻¹): 3418 (O-H), 1654 (C=O).

5,7-Dihydroxy-3-tolyl-4H-chromen-4-one (4f). Yield: 68%, Mp: 193–195°C; Anal. Calcd: for C₁₆H₁₂O₄; C, 71.64; H, 4.51; O, 23.86; found: C, 71.61; H, 4.53; O, 23.87; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.90 (s, 1H, 5-OH), 10.89, (s, 1H, 7-OH), 8.38 (s, 1H, 2-H), 7.46 (d, J = 8.0 Hz, 2H, Ar-H), 7.26 (d, J = 8.0 Hz, 2H, Ar-H), 6.40 (d, J= 2.0 Hz, 1H, Ar-H), 6.24 (d, J = 2.0 Hz, 1H, Ar-H), 2.34 (s, 3H,); ¹³CNMR (DMSO-d₆, 100 MHz): δ 179.9, 164.5, 161.99, 157.5, 157.4, 154.5, 137.3, 128.8, 128.7, 127.8, 122.2, 104.4, 99.0, 93.7, 20.7; ESI-MS: 269 [M + H]⁺; FT-IR (KBr, Cm⁻¹): 3264 (O-H), 3073, (C-H aromatic), 2921 (C-Haliphatic), 1643 (C=O).

3-(4-Bromophenyl)-5,7-dihydroxy-4H-chromen-4-one (4g). Yield: 66%, Mp: 212–214°C; Anal. Calcd for C₁₅H₁₄BrO₅: C, 54.08; H, 2.72; Br, 23.99; O, 19.21; found: C, 54.06; H, 2.73; O, 19.22; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.79 (s, 1H, 5-OH), 10.94, (s, 1H, 7-OH), 8.47 (s, 1H, 2-H), 7.66 (d, J = 8.8 Hz, 2H, Ar-H), 7.55 (d, J = 8.4 Hz, 2H, Ar-H), 6.42 (d, J = 1.6 Hz, 1H, Ar-H), 6.25 (d, J = 1.6 Hz, 1H, Ar-H); ¹³C NMR (DMSO-d₆, 100 MHz): δ 179.5, 164.5, 161.9, 155.1, 131.1, 130.9, 121.3, 121.1, 99.2, 93.8; ESI-MS: 332 [M + H]⁺.; FT-IR (KBr, Cm⁻¹): 3374 (O-H), 3063, (C-H aromatic), 2919 (C-Haliphatic), 1657 (C=O).

3.3.3. Demethylation of 4a (Preparation of 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) (4b)

4a (0.26 gm, 0.91 mmol) suspended in toluene (10 ml) was added to anhydrous AlCl₃ and the mixture was refluxed with string to 160°C for 6 h; after completion of reaction (monitored by TLC), the reaction mixture was cooled and poured into water and acidified with HCl acid to break the AlCl₃; the solution was then filtered, dried, and washed with toluene and purified by column chromatography to yield 4b.

Yield: 84%, Mp: 292–294°C; Anal. Calcd for C₁₅H₁₀O₅: C, 66.67; H, 3.73; O, 29.60; found: C, 66.62; H, 3.76; O, 29.62; ¹H NMR (DMSO-d₆, 400 MHz): δ 12.94 (s, 1 H, 5-OH), 10.9 (s, 1H, 7-OH), 9.61 (s, 1H, 4′-OH), 8.31 (s, 1H, 2-H), 7.38 (d, J = 4.0 Hz, 2H, Ar-H), 6.82 (d, J = 4.0 Hz, 2H, Ar-H), 6.39 (s, 1H, Ar-H); ¹³C NMR (DMSO-d₆, 100 MHz): δ 180.2, 164.2, 161.9, 157.5, 157.4, 153.9, 130.1, 122.2, 121.20, 115.0, 104.4, 98.9, 93.6; ESI-MS: 271 [M + H]⁺.; FT-IR (KBr, Cm⁻¹): 3412 (-OH), 3004, (C-H aromatic), 2933 (C-H aliphatic), 1652 (C=O).

3.3.4. 3-(4-Bromophenyl)-5,7-dimethoxy-4H-chromen-4-one (4h) (Prepared by Methylation of 4g)

To a solution of 4 g (6 mmol) in 10 mL acetone, potassium carbonate (18 mmol) was added and then DMS (15 mmol) was added dropwise and refluxed at 60°C for about 2 h. After completion of the reaction as indicated by TLC, the reaction mixture was filtered and concentrated and the crude product was purified by column chromatography (eluent hexane : ethylacetate, 8 : 2).

Yield: 80%, Mp: 174–176°C; Anal. Calcd for C₁₇H₁₃BrO₄: C, 56.53; H, 3.63; Br, 22.12; O, 17.72; found: C, 56.50; H, 3.64; O, 17.74; ¹H NMR (DMSO-d₆, 400 MHz): δ 7.78 (s, 1H, 2-H), 7.52 (d, J = 8.4 Hz, 2H, Ar-H) 7.43 (d, J = 8.4 Hz, 2H, Ar-H) 6.45 (d, J = 2.4 Hz, 1H, Ar-H), 6.38 (d, J = 2 Hz, 1H, Ar-H), 3.93 (s, 3H), 3.89 (s, 3H); ¹³CNMR (DMSO-d₆, 100 MHz): δ 174.8, 164.1, 161.4, 159.8, 150.4, 130.9, 125.3, 122.1, 109,8, 96.3, 96.2, 92.6, 92.5, 56.0; ESI-MS: 361 [M + H]⁺; FT-IR (KBr, Cm⁻¹): 3002, (C-H aromatic), 2923 (C-H aliphatic), 1657 (C=O).

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References

M. Seeger, M. Gonzáez, B. Cámara et al., “Biotransformation of natural and synthetic isoflavonoids by two recombinant microbial enzymes,” Applied and Environmental Microbiology, vol. 38, pp. 473–51, 2003.
View at: Google Scholar
S. A. Fedoreyev, V. P. Bulgakov, O. V. Grishchenko et al., “Isoflavonoid composition of a callus culture of the relict tree Maackia amurensis Rupr. et Maxim,” Journal of Agricultural and Food Chemistry, vol. 56, no. 16, pp. 7023–7031, 2008.
View at: Publisher Site | Google Scholar
W. De-Eknamkul, K. Umehara, O. Monthakantirat et al., “QSAR study of natural estrogen-like isoflavonoids and diphenolics from Thai medicinal plants,” Journal of Molecular Graphics and Modelling, vol. 29, no. 6, pp. 784–794, 2011.
View at: Publisher Site | Google Scholar
O. Lapcık, M. Hill, R. Hampl, K. Wähälä, and H. Adlercreutz, “Identification of isoflavonoids in beer,” Steroids, vol. 63, no. 1, pp. 14–20, 1998.
View at: Publisher Site | Google Scholar
G. M. Boland and D. M. X. Donnelly, “Isoflavonoids and related compounds,” Natural Product Reports, vol. 15, no. 3, pp. 241–260, 1998.
View at: Publisher Site | Google Scholar
M. A. Rostagno, M. Palma, and C. G. Barroso, “Pressurized liquid extraction of isoflavones from soybeans,” Analytica Chimica Acta, vol. 522, no. 2, pp. 169–177, 2004.
View at: Publisher Site | Google Scholar
R. Liu, Y. Hu, J. Li, and Z. Lin, “Production of soybean isoflavone genistein in non-legume plants via genetically modified secondary metabolism pathway,” Metabolic Engineering, pp. 91–79, 2000.
View at: Google Scholar
K. L. Werner, T. Oliver, W. L. Roman, and S. Helga, “Different Types of Combination Effects for the Induction of Micronuclei in Mouse Lymphoma Cells by Binary Mixtures of the Genotoxic Agents MMS, MNU, and Genistein,” Toxicological Sciences, vol. 86, pp. 318–323, 2005.
View at: Publisher Site | Google Scholar
S. Yun-Hee, P. Sun-Dong, and N. J. Kyung-Soo, “Effective chemopreventive activity of genistein against human breast cancer cells,” Biochemistry and Molecular Biology, vol. 39, p. 451, 2006.
View at: Google Scholar
B. Sanjeev, L. Yiwei, W. Zhiwei, and H. Fazlul, Cancer Letters, vol. 269, pp. 226–242, 2008.
W.-F. Chen, M.-H. Huang, C.-H. Tzang, M. Yang, and M.-S. Wong, “Inhibitory actions of genistein in human breast cancer (MCF-7) cells,” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1638, no. 2, pp. 187–196, 2003.
View at: Publisher Site | Google Scholar
A. Arti, G. Muraleedharan, and M. Gale, “Antioxidant activities of isoflavones and their biological metabolites in a liposomal system,” Free Radical Biology and Medicine, vol. 24, pp. 1355–1363, 1998.
View at: Google Scholar
C. E. Rüfer and S. E. Kulling, “Antioxidant activity of isoflavones and their major metabolites using different in vitro assays,” Journal of Agricultural and Food Chemistry, vol. 54, no. 8, pp. 2926–2931, 2006.
View at: Publisher Site | Google Scholar
A. Arora, M. G. Nair, and G. M. Strasburg, “Antioxidant activities of isoflavones and their biological metabolites in a liposomal system,” Archives of Biochemistry and Biophysics, vol. 356, no. 2, pp. 133–141, 1998.
View at: Publisher Site | Google Scholar
J. H. Mitchell, P. T. Gardner, D. B. McPhail, P. C. Morrice, A. R. Collins, and G. G. Duthie, “Antioxidant efficacy of phytoestrogens in chemical and biological model systems,” Archives of Biochemistry and Biophysics, vol. 360, no. 1, pp. 142–148, 1998.
View at: Publisher Site | Google Scholar
C. H. Lee, L. Yang, J. Z. Xu, S. Y. V. Yeung, Y. Huang, and Z.-Y. Chen, “Relative antioxidant activity of soybean isoflavones and their glycosides,” Food Chemistry, vol. 90, no. 4, pp. 735–741, 2005.
View at: Publisher Site | Google Scholar
L.-N. Zhang, P. Cao, S.-H. Tan, W. Gu, L. Shi, and H.-L. Zhu, “Synthesis and antimicrobial activities of 7-O-modified genistein derivatives,” European Journal of Medicinal Chemistry, vol. 43, no. 7, pp. 1543–1551, 2008.
View at: Publisher Site | Google Scholar
H.-Q. Li, J.-Y. Xue, L. Shi, S.-Y. Gui, and H.-L. Zhu, “Synthesis, crystal structure and antimicrobial activity of deoxybenzoin derivatives from genistein,” European Journal of Medicinal Chemistry, vol. 43, no. 3, pp. 662–667, 2008.
View at: Publisher Site | Google Scholar
M. Nadal-Serrano, D. Pons, J. Sastre-Serra, and M. Blanquer-Rosselló, “Genistein modulates oxidative stress in breast cancer cell linesaccording to ERα/ERβ ratio: Effects on mitochondrial functionality,sirtuins, uncoupling protein 2 and antioxidant enzymes mercedes,” The International Journal of Biochemistry & Cell Biology, vol. 45, pp. 2051–2051, 2013.
View at: Google Scholar
C. Santell, C. Chang, G. Nair, and G. Helferich, “Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats,” Journal of Nutrition, vol. 127, pp. 263–269, 1997.
View at: Google Scholar
W. H. Tolleson, D. R. Doerge, M. I. Churchwell, M. M. Marques, and D. W. Roberts, “Metabolism of biochanin A and formononetin by human liver microsomes in vitro,” Journal of Agricultural and Food Chemistry, vol. 50, no. 17, pp. 4783–4790, 2002.
View at: Publisher Site | Google Scholar
L. Kole, B. Giri, S. K. Manna, B. Pal, and S. Ghosh, “Biochanin-A, an isoflavon, showed anti-proliferative and anti-inflammatory activities through the inhibition of iNOS expression, p38-MAPK and ATF-2 phosphorylation and blocking NFκB nuclear translocation,” European Journal of Pharmacology, vol. 653, no. 1-3, pp. 8–15, 2011.
View at: Publisher Site | Google Scholar
Y. J. Seo, B. S. Kim, S. Y. Chun, Y. K. Park, K. S. Kang, and T. G. Kwon, “Apoptotic effects of genistein, biochanin-A and apigenin on LNCaP and PC-3 cells by p21 through transcriptional inhibition of polo-like kinase-1,” Journal of Korean Medical Science, vol. 26, no. 11, pp. 1489–1494, 2011.
View at: Publisher Site | Google Scholar
K. Polkowski and A. P. Mazurek, “Biological properties of genistein. A review of in vitro and in vivo data,” Acta Poloniae Pharmaceutica. Drug Research, vol. 57, no. 2, pp. 135–155, 2000.
View at: Google Scholar
M. Switalska, G. Grynkiewicz, L. Strzadala, and J. Wietrzyk, “Novel genistein derivatives induce cell death and cell cycle arrest through different mechanisms,” Nutrition and Cancer, vol. 65, no. 6, pp. 874–884, 2013.
View at: Publisher Site | Google Scholar
Y.-W. Kim, J. C. Hackett, and R. W. Brueggemeier, “Synthesis and aromatase inhibitory activity of novel pyridine-containing isoflavones,” Journal of Medicinal Chemistry, vol. 47, no. 16, pp. 4032–4040, 2004.
View at: Publisher Site | Google Scholar
M. Radharani, A. Madhan, A. Ravi, S. Vered, B. U. Christopher, and K. Saeed, Cancer Biology & Therapy, vol. 11, pp. 883–892, 2011.
K. V. Raghava Rao and T. Raghava Rao, “Molecular characterization and its antioxidant activity of a newly isolated Streptomyces coelicoflavus BC 01 from mangrove soil,” Journal of Young Pharmacists, vol. 5, no. 4, pp. 121–126, 2013.
View at: Publisher Site | Google Scholar
B. Frédéric, D. Aline, B. Ahcème et al., “Genistein and fluorinated analogs suppress agonist-induced airway smooth muscle contraction,” Bioorganic & Medicinal Chemistry Letters, vol. 7, pp. 1323–1326, 1997.
View at: Publisher Site | Google Scholar

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Copyright © 2018 Salah Hamza Sherif and BerihuTekluu Gebreyohannes. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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