Synthesis, Characterization and Antimicrobial Activity of Novel Chalcones from 1-[4-(1H-imidazol-1-yl) Phenyl] Ethanone

 

Gondu Eswara Rao¹*, S.A. Rahaman², A. Prameela Rani³, Ch. M.M. Prasada Rao⁴

¹Assistant Professor, NRI College of Pharmacy, Pothavarapadu Village, Agirapalli (M) A.P.

²Professor, Nirmala College of Pharmacy, Atmakur Village, Mangalagiri Mandal, Guntur Dt, A.P - 522 503

³Principal & Professor, ANU College of Pharmaceutical Science, Nagarjuna Nagar, Acharya Nagarjuna University, Guntur-530 003, (A.P), India.

⁴Assistant Professor, QIS College of Pharmacy, Vengamukkala Palem, Ongole, A.P-523272.

*Corresponding Author E-mail: eswar_gondu@yahoo.com

 

Chalcones were synthesized by condensing 1-[4-(1H-imidazol-1-yl) phenyl] ethanone with aromatic aldehydes derivatives in dilute ethanolic sodium hydroxide solution at room temperature according to Claisen-Schmidt condensation. All these compounds were characterized by means of their IR, ¹H NMR spectroscopic data and microanalyses. The antimicrobial activity of these compounds was evaluated by the cup plate method.

 

INTRODUCTION:

Discovery of novel synthetic heterocyclic compounds are the target of organic scientists to cure the diseases. Hence, novel chalcones were synthesized because it is known to exhibit various biological activities. Chalcones have been reported to possess antioxidant ^[1-3], antiulcer ^[4],  antimalarial ^[5,6], antileishmanial ^[7], anti-inflammatory ^[8], antitumor ^[9], ant tubercular ^[10,11] and antibacterial activity ^[12] and antifungal activity. The presence of a reactive     α,β- unsaturated keto functional group in chalcones is found to be responsible for their antimicrobial and other activities, which may be altered depending on the type and position of substituent on the aromatic rings. In the present communication we report the reaction of 1-[4-(1H-imidazol-1-yl) phenyl] ethanone with different aromatic aldehydes to afford novel chalcones (1-5). The structures of the various synthesized compounds were assigned on the basis of elemental analysis, IR and ¹H NMR spectral data. These compounds were also screened for their antibacterial and antifungal activities.

 

EXPERIMENTAL WORK:

Melting points were determined on a capillary melting point apparatus and are uncorrected. 1H NMR spectra was recorded in the indicated solvent on Bruker AV 400 MHz spectrometer using TMS as internal standard. Infrared spectra were recorded in KBr on Perkin-Elmer AC-1 spectrophotometer. Microanalyses were performed on Carlo Erba EA145 1108 element analyzer and were within the ± 0.5% of the theoretical values. Column chromatography was performed on silica gel (Merck, 60-120 mesh).

 

Procedure:^13-15

A mixture of 1-[4-(1H-imidazol-1-yl) phenyl] ethanone (0.0025mole) and aryl aldehyde (0.0025mole) was dissolved in 8mL methanol. To this 1 mole of 40% NaOH was added. The mixture was stirred at room temperature for an half an hour and kept aside for 12hrs. Then the reaction mixture was poured over crushed ice and acidified with equal ratio of Conc. HCl and water. The obtained yellow solid was filtered through vacuum filtration, washed with distilled water and dried. (Scheme 1). The Characterization data of these compounds is described in Table 1.

 

 

SCHEME -I

 

 

Spectral data:

(1-[4-(1H-imidazol-1-yl)phenyl]-3-(2,4,6-trimethoxyphenyl) prop-2-en-1-one)

IR(cm-1) C-H str --- 3131.7, C=O str --- 1678.3, C=C str --- 1600.7; 1H NMR(300 MHz, CDCl₃, δppm) 7.12(1H, d,J=8Hz, C-2H),7.387(1H, d, J=8Hz, C-3H), 7.656-7.8 ( aromatic protons), 3.225-3.87 (OCH₃- 9H).

 

1-[4-(1H-imidazol-1-yl) phenyl]- 3-(3,4,5-trimethoxy phenyl)prop-2-en-1-one

IR(cm-1) C-H str --- 3131.7, C=O str --- 1678.3, C=C str --- 1600.7; 1H NMR(300 MHz, CDCl₃, δppm) 7.12(1H, d, J=8Hz, C-2H),7.387(1H, d, J=8Hz, C-3H), 7.656-7.8   aromatic protons) , 3.225-3.87 (OCH₃- 9H).

 

1-[4-(1H-imidazol-1-yl) phenyl]- 3-[4-(methylsulfanyl) phenyl]prop-2-en-1-one

IR(cm-1) C-H str --- 3131.7, C=O str --- 1678.3, C=C str --- 1600.7; 1H NMR(300 MHz, CDCl₃, δppm) 7.12(1H, d, J=8Hz, C-2H),7.387(1H, d, J=8Hz, C-3H), 7.656-7.8 (aromatic protons), 3.225-3.87 (CH₃- 3H) .

 

1-[4-(1H-imidazol-1-yl) phenyl]- 3-(2,4,6-trimethyl phenyl)prop-2-en-1-one

IR(cm-1) C-H str --- 3131.7, C=O str --- 1678.3, C=C str --- 1600.7; 1H NMR(300 MHz, CDCl₃, δppm) 7.12(1H, d,J=8Hz, C-2H),7.387(1H, d, J=8Hz, C-3H), 7.656-7.8 (aromatic protons), 3.225-3.87 (OCH₃- 9H) .

 

1-[4-(1H-imidazol-1-yl) phenyl] - 3-(2, 3, 4-trimethoxy phenyl)prop-2-en-1-one

IR(cm-1) C-H str --- 3131.7, C=O str --- 1678.3, C=C str --- 1600.7; 1H NMR(300 MHz, CDCl₃, δppm) 7.12(1H, d, J=8Hz, C-2H),7.387(1H, d, J=8Hz, C-3H), 7.656-7.8 (aromatic protons), 3.225-3.87 (OCH₃- 9H).

Antibacterial activity of synthesized compounds

The antimicrobial activity was tested by Cup plate method^[16-19] using Mueller- Hinton agar medium was employed to study the preliminary antibacterial activity of novel chalcones (1-5) against Staphylococcus aureus, Bacillus substilis, Proteus vulgaris and E.coli.

 

Preparation of nutrient agar medium

The agar medium was purchased from HI media Laboratories Ltd., Mumbai, India. Peptone, meat extract and sodium chloride were dissolved in 100 ml of distilled water and the solution was made up to 200 ml by distilled water. The pH of the medium was adjusted to 7.2. Agar was dissolved in above solution. Then the solution was distributed in 20 ml quantities into 50 ml boiling test tubes. They were sterilized in autoclave at temperature of 121⁰c and pressure of 15 lbs/sq. in for 20 minutes.

 

Procedure

The above medium was inoculated at 1% level with 18 hrs old cultures of the above mentioned test organisms and were transferred into sterile petridishes (6 inch). The medium in the plates was allowed to set at room temperature for about 10 minutes and they were solidifying in a refrigerator for 30 minutes. Then three bores were made in each petriplate and respective 1 ml test and standard concentrations of prepared 50μg/ml, 100μg/ml prepared in DMSO were poured. The plates thus prepared were left to stand in a refrigerator for about 1 hr to allow the test solution for diffusion. Then incubation of the above plates was done for 24 hrs at 37⁰c. The plates were examined for zones of inhibition and the inhibition zone diameters were recorded in table 2

 

TABLE:- 1 Characterization data of Synthesized Compounds

Compound	M.F	M.P(oC)	% Yeild	ELEMENTAL ANALYSIS
				C		H		O
				FOUND	CAL	FOUND	CAL	FOUND	CAL
1	C21H20N2O4	121	87	69.97	69.22	5.62	5.53	7.72	7.69
2	C21H20N2O4	112	84	69.97	69.22	5.62	5.53	7.72	7.69
3	C19H16N2OS	135	88	71.48	71.22	5.12	5.03	8.78	8.74
4	C21H20N2O	126	82	79.23	79.22	6.45	6.37	8.92	8.85
5	C21H20N2O4	124	94	69.77	69.22	5.62	5.53	7.72	7.69

 

TABLE:- 2 ANTI MICROBAIL ACTIVITY VALUES:

COMPOUNDS	B. subtilis		S. aureus		P. vulgaris		E.coli
	50μg/ml	100μg/ml	50μg/ml	100μg/ml	50μg/ml	100μg/ml	50μg/ml	100μg/ml
1	15	17	13	17	15	18	14	20
2	21	24	23	27	22	25	23	28
3	20	22	19	23	21	24	20	24
4	13	16	14	16	11	15	14	18
5	17	20	16	19	18	21	18	22
Streptomycin	24	28	25	28	29	32	27	31

 

 

RESULTS AND DISSCUSION: ^{17- 20}

Five novel 1-[4-(1H-imidazol-1-yl) phenyl] ethanone chalcones were designed and synthesized by the condensation of 1-[4-(1H-imidazol-1-yl) phenyl] ethanone with various aromatic aldehydes in dilute ethanolic potassium hydroxide solution at room temperature. The molecular formulas of the compounds were found by Carlo Erba elemental analyzer. The yields of novel chalcones    (1-5) were found to be 82 – 94 % as shown in Table 1.

 

The obtained compound structures were characterized by its IR and ¹H NMR spectral data. The obtained Compounds were screened for antibacterial activities at the concentrations of 50, 100 μg/ml. Among all tested compounds only 1-[4-(1H-imidazol-1-yl) phenyl]- 3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one showed maximum zone of inhibition when comparable with standard antibacterial agent Streptomycin as shown in Table 2.

 

CONCLUSION:

The screening results revealed that the synthesized chalcones containing of methoxy groups at alternative arrangement have showed significant antibacterial and antifungal activity at 50 μg/ml, 100 μg/ml dose levels and are comparable to that of standard drug streptomycin.

 

ACKNOWLEDGEMENT:

We are grateful to Management of Nirmala College of Pharmacy for providing research facilities to carry out research work. Authors are also thankful to Lila implex Limited for providing IR, 1HNMR spectral data.

 

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Received on 08.06.2013       Modified on 18.06.2013

Accepted on 24.06.2013      © AJRC All right reserved