Synthesis of Chalcones and Evaluation of Their Anti-Microbial Activity

P. Parveen¹*, P. Usha¹, V. Vasu Naik¹, Sk. Shaheda Sultana¹, M. Gayatri Ramya²

¹Hindu College of Pharmacy, Amaravathi Road, Guntur-522002

²University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur-500510

*Corresponding Author E-mail: pothukantiparveen@gmail.com

ABSTRACT:

Chalcones are main precursor for biosynthesis of flavonoids which are frequent components of human diet. Recent studies on biological evaluation of chalcones revealed some Anticancer, Anti inflammatory, Anti mitotic, Anti tubercular, Cardiovascular, cell differenciation inducing, nitric oxide regulation modulatory and hyperglycaemic activities. This present research includes synthesis of varies chalcones from 5-acetyl salicylamide and evaluation of their anti microbial activity.

Objective

1. To synthesize chalcones using different catalyst solid NaOH.

2. Characterize chalcones using TLC, NMR, MASS and IR spectrometry.

3. To evaluate the anti-microbial activity .

KEYWORDS:

INTRODUCTION:

Chalcones, 1,3-diaryl-2-propen-1-ones Consists of two un substituted aromatic rings separated by three carbons of which two are connected by double bond and the third is by carbonyl group. The presence of reactive α,β-unsaturated keto functional group is responsible for their activity.

Background of study:

Chalcone is an aromatic ketone , Other names for chalcone are benzyl acetophenone and phenyl styryl ketone. Chalcone can be prepared by an aldol condensation between a benzaldehyde and an acetophenone in the presence of a catalyst. Azachalcones, isoliquiritigenin are some chalcones.

LITERATURE REVIEW:

Anti - Inflammatory Activity:

Rajendra Prasad et al., reported a series of 4’-amino chalcones were synthesized by claisen-schemidt condensation of 4-amino acetophenone with various substuted aromatic aldehydes.

Horng- Huey Ko, et al., reported the synthesis and biological evaluation of 2’,5’-Dialkoxy chalcone. These compound inhibit the nitric oxide production and act as an anti-inflammatory agents.

R₃=H;R₅’,R₂,=OCH₃;R₄=OH

Anti-Hepetotoxic Activity:

Shan Alamkhan et al., reported the synthesis of chalcones containing 1,4-dioxane ring.

Anti-Platelet Activity:

Li-Ming Zhao et al., reported a series of trihydroxy chalcones

Anti-Hyperglycemic Activity:

Chalcones, a new series of glycosidase inhibitors, were synthesize the amino chalcones were by investigated (Woo Duck Seo et al 2005).

ANTI-BACTERIAL ACTIVITY:

Mahammad Azad et al ., reported a series of quinoline based chalcones.

Present work:

Synthesis of Chalcones Using 5-Acetyl Salcylamide

SYNTHESIS OF CHALCONES:

Procedure:

To the solution of 5-acetyl salicylamide (0.01) and aromatic aldehyde (0.01) in 25ml methanol was added with 10% NaoH. This reaction mixture was stirred for 3-4hours at room temperature. This reaction mixture was treated with ice cold water and then acidified with concentrated HCL. The product was separated out and washed with cold water and purified by recrystallization from suitable solvents (methanol and ethyl acetate in 1:1 ratio).

Recrystalization from suitable solvents (methanol and ethyl acetate in 1:1 ratio)

S.No	Starting material		Aldehyde ®	Chalcone
1		5-acetyl salicylamide	3,4,5trimethoxy benzaldehyde	3,4,5 Trimethoxy,1-amido,2-hydroxy diphenyl styryl ketone.
2		5-acetyl salicylamide	salicylaldehyde	2-hydroxy,1-amido,2-hydroxy diphenyl styryl ketone.
3		5-acetyl salicylamide	p-chloro benzaldehyde	P-chloro,1-amido,2-hydroxy diphenyl styryl ketone.
4		5-acetyl salicylamide	4-dimethyl amino benzaldehyde	4-dimethyl amino,1-amido,2-hydroxy diphenyl styryl ketone.
5		5-acetyl salicylamide	p-methoxy benzaldehyde	P-methoxy,1-amido,2-hydroxy diphenyl styryl ketone.
6		5-acetyl salicylamide	2-chloro benzaldehyde	2-Chloro,1-amido,2-hydroxy diphenyl styryl ketone.
7		5-acetyl salicylamide	cinnamaldehyde	1-propene,1-amido,2-hydroxy diphenyl styryl ketone.

Physical data

Compound	melting point	Molecular formula	TLC
3,4,5 Trimethoxy,1-amido,2-hydroxy diphenyl styryl ketone.	202⁰C	C₁₉H₁₉O₆N		0.56
2-hydroxy,1-amido,2-hydroxy diphenyl styryl ketone.	205⁰C	C₁₆H₁₃O₄N		0.67
P-chloro,1-amido,2-hydroxy diphenyl styryl ketone.	210⁰C	C₁₆H₁₂0₃NCl		0.78
4-dimethyl amino,1-amido,2-hydroxy diphenyl styryl ketone.	213⁰C	C₁₈H₁₈0₃N		0.62
P-methoxy,1-amido,2-hydroxy diphenyl styryl ketone.	215⁰C	C₁₇H₁₅O₄N		0.45
2-Chloro,1-amido,2-hydroxy diphenyl styryl ketone.	217⁰C	C₁₆H₁₂O₃NCl		0.53
1-propene,1-amido,2-hydroxy diphenyl styryl ketone	219⁰C	C₁₈H₁₅0₃N		0.48

Characterization of Compounds

Infra Red Spectroscopy

IR Spectrum is important record gives information about structure of organic compound. This technique provide a spectrum containing a large number of absorption band. When IR spectrum is passed through the sample molecular vibrations are seen. There are 2 types of molecular vibrations

1. Bending vibrations

2. Stretching vibrations

S.no	chalcone	C=0		C=C		Ar-H
1.	3,4,5Trimethoxy,1-amido,2-hydroxy,diphenylstyryl ketone		1637.29		1550.19		3366.17
2.	2-hydroxy,1-amido,2-hydroxy diphenyl styryl ketone		1554.72		1407.27		3365.06
3.	p-chloro,1-amido,2-hydroxy diphenyl styryl ketone		1632.33		1552.15		3372.54
4	4-dimethyl amino,1-amido,2-hydroxy diphenyl styryl ketone		1588.03		1549.50		3373.51
5.	P-methoxy,1-amido,2-hydroxy diphenyl styryl ketone		1625.63		1546.47		3368.57
6.	2-Chloro,1-amido,2-hydroxy diphenyl styryl ketone		1629.06		1549.50		3366.09
7.	1-propene,1-amido,2-hydroxy diphenyl styryl ketone		1637.42		1551.35		3360.94

IR Spectrum Of 3,4,5Trimethoxy,1-amido,2-hydroxy,diphenylstyryl ketone

IR Spectrum of 2-hydroxy,1-amido,2-hydroxy diphenyl styryl ketone

IR Spectrum of p-chloro,1-amido,2-hydroxy diphenyl styryl ketone

IR spectrum of 4-dimethyl amino,1-amido,2-hydroxy diphenyl styryl ketone

IR Spectrum of P-methoxy,1-amido,2-hydroxy diphenyl styryl ketone

IR Spectrum of 2-Chloro,1-amido,2-hydroxy diphenyl styryl ketone

IR Spectrum of 1-propene,1-amido,2-hydroxy diphenyl styryl ketone

NMR SPECTROSCOPY:

It is study of spin changes at nuclear level radio frequency energy is absorbed in presence of magnetic field.When energy in form of radio frequency is applied.Applied frequency is equal to processional frequency absorption of energy occurs and NMR signal is recorded.

NMR Spectrum of 3,4,5 Trimethoxy,1-amido,2-hydroxy diphenyl styryl ketone.

Mass Spectroscopy

Determines molecular weight of compounds.

Zone of inhibition for 24hrs (in mm):

COMPOUND	Concⁿ	*Bacillus subtius*	*Aspergillus* *niger*
3,4,5Trimethoxy,1-amido,2hydroxy,diphenylstyryl ketone	100mcg/ml	6mm	5mm
2-Chloro,1-amido,2-hydroxy diphenyl styryl ketone	100mcg/ml	04mm	03mm
1-propene,1-amido,2-hydroxy diphenyl styryl ketone	100mcg/ml	03mm	02mm
4-dimethyl amino,1-amido,2-hydroxy diphenyl styryl ketone	100mcg/ml	04mm	01mm
2-hydroxy,1-amido,2-hydroxy diphenyl styryl ketone	100mcg/ml	04mm	03mm
STANDARD (amoxicillin)	100mcg/ml	5mm	5mm

CONCLUSION:

In the present study all synthesized compounds tested for anti bacterial activity and have shown significant activity when compared with standard drug Amoxicillin. But as biological and pharmacological screening conducted was only the preliminary results and the further structural modification and screening has to be done to confirm the more potent activity better activity.

However it is an interesting field of study which can be taken for more systematic studies under controlled conditions.

REFERENCES:

1. Abdullah M. Asiri and Salman A. Khan ; (2011) ," Synthesis and Anti-Bacterial Activities of a Bis- Chalcone Derived from Thiophene and Its Bis- Cyclized Products", Molecules, 16, 523-531

2. Rane, R.A.; Telekar, V.N; (2010) "Synthesis and evaluation of novel chloropyrrole molecules designed by molecular hybridization of common pharmacophores as potential antimicrobial agents" . Bioorg. Med. Chem. Lett , 20, 5681-5685.

3. Kumar, D.; Kumar, N.M.; Akamatsu, K.; Kusaka, E.; Harada, H.; Ito, T; (2010) "Synthesis and biological evaluation of indolyl chalcones as antitumor agents" . Boorg. Med. Chem. Lett., 20, 3916-3919.

4. Ducki, S.; Forrest, R.; Hadfield, J.A.; Kendall, A.; Lawrence, N.J.; McGown, A.T.; Rennison, D. Potent ; (1998) " antimitotic and cell growth inhibitory properties of substituted chalcones". Bioorg. Med. Chem. Lett , 8, 1051-1056.

5. Edenharder, R.; Petersdorff, I.V.; Rauscher, R.; (1993)." Antimutagenic effects of flavoniods, chalcones and structurally related compounds on the activity of 2-amino-3-methylinidazo[4,5-ƒ]quinoline (IQ) and other heterocyclic amine mutagens from cooked food". Mutat. Res., 287, 261-274.

6. P. Prasanna Raja , M.S. Riyazulah, V. Siva Kumar ;(2010) "Synthesis and Biological Evaluation of some Chalcone Derivatives". ChemTech Res ,2(4)

7. Urmila Gupta, Vineeta Sareen, Vineeta Khatri, Sanjana Chugh,(2005) " Synthesis and antifungal activity of new Fluorine containing 4- (substituted Phenyl azo) Pyrazoles and Isoxazoles", Indian J. Of Het. Chem ; 14: 265-266

8. Pandey V.K., Gupta V.D. and Tiwari D.N., (2004) " Synthesis of Substituted Benzoxazines as potential Antiviral agents", Indian J. of Het.Chem., 13, 399-400

9. Solankee. A , Patel .K , and Patel. R. A, (2012) " Facile Synthesis and Studies of Some New Chalcones" , E-Journal of Chemistry , 9(4), 1897- 1905

10. B. Anupama , Subas Chandra Dinda, Y. Rajendra Prasad and A. Vasudeva Rao, (2012) "Synthesis and antimicrobial Activity of somenew2,4,6-trisubstituted Pyrimidines" , IJRPC , 2(2) .

11. M.V. Jyothi , Y. Rajendra Prasda, P. Venkatesh and M. Sureshreddy,(2012)

Received on 19.09.2013 Modified on 15.11.2013

Res. J. Pharm. Dosage Form. & Tech. 6(1): Jan.-Mar. 2014; Page 26-32