Synthesis and Antioxidant Activity of Some Flavone Derivatives

Chandrahas N Khobragade¹*, Ragini G Bodade¹ and Anand V. Manwar ²

¹School of Life Sciences, Swami Ramanand Teerth Marathawada University, Nanded-431606, India

²Department of Microbiology, Dyanopasak Mahavidyalaya, Parbhani -431401, India

*Corresponding Author E-mail:  cnkhobragade@rediffmail.com

ABSTRACT:

Some novel flavones were synthesized by condensation reactions of substituted ketones with substituted aldehydes to form chalcones. The formed 2-hydroxyl substituted chalcone made to react with polyethylene glycol-400 (PEG-400) with catalytic amount of iodine, produces flavone derivatives. The synthesized derivatives were characterized by spectral analysis and revealed to be therapeutically active as antioxidant agents.

KEYWORDS: Synthesis, Flavones, Antioxidant activity.

INTRODUCTION:

Flavonoids are widely distributed phytochemicals classified as anthocyanidins, flavonols, Chalcones, aurones, flavanone, Isoflavones, flavans, flavanonols, flavanols and flavones with difference in their structural group arrangements¹.  In vitro study of flavonoids confirms the antifungal, antibacterial, antiviral, anti-spasmodic, anti-anginal, anti-hepatotoxic, anti-inflammatory and anti-allergic activities ².  Recently flavonoids and chalcones are found to be effective as antituberculosis agents ³. A number of medicinal plants with active flavonoids contents are screened and used to treat the disorders like cancer, Alzheimer disease, diabetics, stroke and atherosclerosis ⁴. Generation of reactive oxygen species (ROS) of biochemical and metabolic processes is supposed to be one of the reasons leading to above mentioned diseases. Pharmacological effects of flavonoids for treating these diseases are linked to their antioxidant or free radical scavenging abilities and interaction with enzyme and other biomolecules. Current research is directed towards finding the antioxidant with enhanced activity and reduced toxicity for treating the diseases^{5, 6}.

Hence, keeping these reports in view, herein we report in this paper the synthesis and biological evaluation of some flavone derivatives for their antioxidant activity.

MATERIALS AND METHODS:

All reagents used in the study were of analytical grade purchased from HiMedia Laboratories Prv. Ltd. and used without further purification. Melting points were determined using Kofler micro melting point apparatus and were uncorrected. IR and NMR data was analyzed by FTIR (Perkin Elmer model RXI spectrophotometer) and AVANCE 300 MHz spectrophotometer in DMSO-d₆ using TMS as an internal standard respectively. The purity of the compounds was tested by ascending thin layer chromatography (TLC) on silica gel G coated glass plates, visualized by iodine vapors.

General procedure for the synthesis of 1-(substitutatedphenyl)-3-[3-( substitutedphenyl)-1- phenyl-1H-pyrazol-4-yl-2-propen1one]:

A mixture of substituted acetophenone (1mmole), 1-phenyl-3-(4- substitutedphenyl) - pyrazolo-4-carbaldehyde (1mmole) and KOH (2mmole) in PEG-400 was stirred at room temperature for 1 h. The product was isolated by acidification with cold dil. HCl, solid separated out, filtered and crystallized from aqueous acetic acid to yield 1(a-f).

General procedure for the synthesis of 2-(1’–phenyl – 3-aryl-1H-pyrazol-4-yl)-flavone 2.

Flavones were synthesized by dissolving   2^'-Hydroxy substituted chalcone (0.416 gm) in 15 mL of poly ethylene glycol (PEG-400) and treated with catalytic amount of iodine (10 mg). Whole contents were heated at 140 ⁰C for 3 h in oil bath. After overnight incubation the product was washed with cold water, followed by 10 % sodium thiosulfate solution for several times. The precipitated flavone was collected and purified by preparative TLC over silica gel G using petroleum ether: ethyl acetate (8:2) as developing solvent. 

Scheme 1.  General synthetic pathway for the preparation of Flavone derivatives.

The compound was purified by recrystallization from methanol after treatment with ice cold water and sodium thiosulphate (10 %). This typical experimental procedure was used to prepare the other analogues of this series (Scheme 1). Thin layer chromatography (TLC) and melting point (M.P.) of all the flavones were checked for confirming their purity.  All the compounds were characterized on the basis of IR and NMR spectral data ⁷.

Evaluation of Antioxidant activity:

The compounds 2 (a-f) were evaluated for their in vitro free radical scavenging activity by the diphenyl picryl hydrazyl (DPPH) assay method⁸. For comparative study the butylated hydroxyl anisole (BHA) was used as standard. The inhibitory concentration (IC₅₀) value representing the concentration required to exhibit 50 % antioxidant activity was extrapolated from the graph plotted

with the % antioxidant activity (AA%) on the y axis and concentration on the x axis (Table 2) .

RESULTS AND DISCUSSION:

An equimolar mixture of substituted acetophenone with 1-phenyl-3-(4- substitutedphenyl) - pyrazolo-4-carbaldehyde (1 mmole) by alkaline condensation with PEG-400 gave the corresponding chalcone 1(a-f). Further 2-hydroxy substituted chalcones on reaction with PEG-400 with catalytic mount of iodine produce the target compounds as suggested in Scheme1. A series of six flavones were synthesized and characterized by IR and 1 ^HNMR analysis ⁷. This confirms the successful synthesis of compounds. The characterization of the compounds is as per Table 1.

Table-1. Charecterization of flavone derivatives 2 (a-f)

Compound	Mol Formula	Substituents				Molecular weight	M.P. ^0C	Yield
		R1	R2	R3	R4
2a	C24H15Cl N2O3	H	H	Cl	OH	414.08	210	85
2b	C28H22Cl2N2O2	H	CH3	Cl	Cl	488.11	195	85
2c	C24H14Cl2N2O2	H	H	Cl	Cl	432.04	212	80
2d	C24H15BrCl2N2O2	Br	H	Cl	Cl	511.97	182	80
2e	C24 H16  N2 O3	H	H	H	OH	380.12	230	90
2f	C28 H24  N2 O3	H	H	CH3	OH	436.18	196	85

Strong free radicals scavenging activities of flavonoids are associated with its structure such as conjugated double bonds and free –OH groups in aromatic ring ⁸. The antioxidant activity study of the synthesized compounds revealed that compound 2e and 2f, substituted with  hydroxyl groups showed best free radical scavenging activity near to the standard BHA, followed by 2a, 2b  and 2c which showed comparable activity. Compound 2d does not give any promising result as represented in Table 2.

Table -2. Antioxidant activity of Compounds 2 (a-f)

Compound No.	IC50^b  ( µg/ml )
2a	85 ± 0. 66
2b	88± 0. 70
2c	93.2± 0. 78
2d	136.5± 0. 82
2e	62.9± 0. 75
2f	71.6± 0. 79
BHA^a	42.32 ± 0. 85

^aStandard Substance    ^bMean ± SD , n= 3

CONCLUSION:

The present study therefore leads to the conclusion that the application of flavone ring can be utilized to develop the highly selective drugs in medical investigations against oxidative stress diseases.

ACKNOWLEDGMENT:

The authors are thankful to Head, School of Life Sciences, SRTM University, Nanded for providing necessary facilities and fanatical support. The data have been generated as a part of the routine work of an organization.

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Received on 06.10.2009        Modified on 25.11.2009

Accepted on 27.12.2009        © AJRC All right reserved

Asian J. Research Chem. 3(1): Jan.-Mar. 2010; Page 139-141