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Asian J. Research Chem. 1(2): Oct.-Dec. 2008.

ISSN 0974-4169

www.ajrconline.org

RESEARCH ARTICLE

Design and Synthesis of Some Novel Chalcones as Potent Antimicrobial Agent


Bhagyesh Baviskar*1, Sureshbhi Patel1, Bhushan Baviskar2, SS Khadabadi2 and Mahendra Shiradkar3.
2 1

Department of Chemistry, S. P. D.M. Art, Science, Commerce College, Shirpur 425 405, (M.S.), India. Department of Pharmaceutical Chemistry, Government College of Pharmacy, Amravati 444 604, (M.S.), India. 3 Sai Adventerium Pharmaceutical Ltd, Hydrabad, (A.P.), India. *Corresponding Author E-mail: baviskarbhushan@gmail.com

ABSTRACT
Some novel chalcones were synthesized by condensation of N-(4-phenylthiazol-2-yl) acetamide with aromatic aldehydes in presence of aqueous potassium hydroxide solution at room temperature. All the title compounds characterized on the basis of their IR, 1H NMR spectroscopic data and elemental analysis. All the compounds have been screened for antimicrobial activity by the cup-plate method.

KEY WORDS INTRODUCTION:

Synthesis, Thiazole, Chalcones, Aldehydes, Antimicrobial activity.

EXPERIMENTAL:
The melting points were recorded on electrothermal apparatus and are uncorrected. IR spectra were recorded in KBr on a perkin-Elmer model-983. 1HNMR spectrum recorded on Varian Mercury 300MHz instrument using CDCl3, DMSO-d6 as solvent (chemical shift in ppm), using TMS as internal standard. Elemental analysis was performed on a Heracus CHN analyzer and was within the 0.5% of the theoretical values. General procedure for the preparation of Thiazolylchalcones 3a-h 4-phenylthiazol-2-amine(1) have been prepared as per reported method.12 Synthesis of N-(4-phenylthiazol-2-yl))acetamide (2) :Dissolve 4-phenylthiazol-2-amine (1) (0.01mole) in chloroform (50ml) and acetylchloride (0.01mole) was added drop wise with constant stirring at 0-5 0C. The reaction mixture was stirred for 8 hrs. The excess solvent was distilled off and the solid product was filtered, dried and recrystallised from ethanol to give compound 2, yield 75%, m.p.: 210-2120C. Anal. Calcd. for C11H10N2OS: C,60.53; H, 4.62; N, 12.83. Found: C, 60.49; H, 4.56; N, 12.78. IR (KBr, cm-1): 3245 (NH), 1621 (C=N), 1678(-NHCOCH3) 635(C-S). Synthesis of N-(4-phenylthiazol-2-yl)cinnamamide(3a):Dissolve N-(4-phenylthiazol-2-yl))acetamide (2) (0.01mole) in ethanol (30ml) and various aromatic aldehydes (0.01mole) were taken and then an aqueous solution of KOH (2%, 5ml) added to it. The reaction mixture refluxed for 5 hrs and then the solvent was removed by vacuum

Due to the rapid development of bacterial resistance to antibacterial agents, it is vital to discover novel scaffold for the design and synthesis of the new antibacterial agents to help in the battle against pathogenic microorganisms. Much research has been carried out with the aim to discover the therapeutic values of thiazole derivatives. A large number of substituted thiazole derivatives are prepared and tested for variety of biological properties1 such as antimicrobial activity2,3. Chalcones represent an essential group of natural as well as synthetic products and some of them possess wide range of pharmacological activity such as antibacterial4, antitumour5, anticancer6, antitubercular7, anti8 inflammatory , antioxidant9, antimalarial10, antileishmanial11 etc. The presence of reactive , unsaturated keto group in chalcones is found to be responsible for their biological activity. In the present work chalcones have been prepared according to claisen-schimidt condensation by condensing ketone with different aromatic aldehydes. The structures of the synthesized compounds were elucidated on the basis of their elemental analysis, IR, 1H NMR spectroscopic data. These compounds were also screened for their antimicrobial activity.

Received on 08.11.2008 Accepted on 15.12.2008

Modified on 30.11.2008 AJRC All right reserved

Asian J. Research Chem. 1(2): Oct.-Dec. 2008; Page 67-69

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Asian J. Research Chem. 1(2): Oct.-Dec. 2008. ,

Table 1. Physical data of compounds 3a-h R M.F. Comp 3a 3b 3c 3d 3e 3f 3g 3h C6H5 3-NO2C6H4 4-N(CH3)2 C6H4 4-OCH3 C6H4 3,4,5-(OCH3)2 C6H4 4-OHC6H4 3-BrC6H4 3-FC6H4 C18H14N2OS C18H13N3O3S C20H19N3OS C19H16N2O2S C21H20N2O4S C18H14N2O2S C18H13BrN2OS C18H13FN2OS

M.P. 0 C 155 165 167 150 160 135 148 140


1

Yield % 75 78 75 80 78 82 85 80

Elemental analyses, % C H N Found Calcd Found Calcd Found Calcd 70.51 70.56 4.55 4.61 9.08 9.14 61.49 61.53 3.70 3.73 11.90 11.96 68.70 68.74 5.40 5.48 12.00 12.02 67.80 67.84 4.72 4.79 8.27 8.33 63.58 63.62 5.02 5.08 7.01 7.07 67.01 67.06 4.40 4.38 8.65 8.69 56.05 56.11 3.35 3.40 7.25 7.27 66.61 66.65 4.01 4.04 8.60 8.64

Table 2. Spectral datd of the compounds 3a-3f Compd. IR (Cm-1, KBr) 3a 635(C-S), 1609(C=N), 1545(-NH), 1735(C=O), 1630(-CH=CH-) 3b 637(C-S), 1608(C=N), 1548(-NH),1732 (C=O), 1622(-CH=CH-),1578(-NO2) 3c 634(C-S), 1607(C=N), 1546(-NH),1725(C=O), 1648(-CH=CH-), 1321(-N(CH3)2 3d 637(C-S), 1611(C=N), 1543(-NH),1743(C=O), 1638(-CH=CH-), 2830(-OCH3) 3e 634(C-S), 1608(C=N) 1550(-NH),1724(C=O), 1620(-CH=CH-), 2825(-OCH3) 3f 3260(-NH-Benzimidazole), 1547(-NH), 1730(C=O), 1645(-CH=CH-), 3450(-OH)

H NMR (CDCl3/DMSO-d6, ppm) 5.21(1H,s,-NH),6.19(1H,s,-CH-thiazole), 6.68(1H,d,-CO-CH=), 7.05(1H,d,=CH-Ar), 7.14-7.50 (10H, m, Ar-H). 5.23(1H,s,-NH),6.18(1H,s,-CH-thiazole), 6.41(1H,d,-CO-CH=), 7.09(1H,d,=CH-Ar),7.20-7.60 (9H, m, Ar-H) 5.20(1H,s,-NH),6.22(1H,s,-CH-thiazole), 6.83(1H,d,-CO-CH=), 7.76(1H,d,=CH-Ar), 2.87(6H,s,N-CH3) 7.22-7.65 (9H, m, Ar-H). 5.25(1H,s,-NH),6.23(1H,s,-CH-thiazole), 6.87(1H,d,-CO-CH=), 7.72(1H,d,=CH-Ar), 3.63(3H,s,-OCH3) 7.25-7.69 (9H, m, Ar-H). 5.20(1H,s,-NH),6.20(1H,s,-CH-thiazole), 6.41(1H,d,-CO-CH=), 7.75(1H,d,=CH-Ar),3.89-3.93(9H,s,-OCH3),7.25-7.68(7H,m,Ar-H). 5.22(1H,s,-NH), 6.22(1H,s,-CH-thiazole), 6.68(1H, d,-CO-CH=), 7.09(1H,d,=CH-Ar),9.83(1H,s,-OH), 7.20-7.60 (9H,m,Ar-H).

Table 3. Antimicrobial and Antifungal Data of compounds 3a-h Compds. R Antifungala Antibacteriala S.a. P.a. E.c. S.t. A.n. C.a. 3a C6H5 13 12 14 10 10 09 3b 2-NO2C6H4 07 08 11 09 12 10 3c 4-N(CH3)2 C6H4 08 09 10 07 13 11 3d 4-OCH3 C6H4 14 12 16 12 10 12 3e 3,4,5-(OCH3)2 C6H4 09 07 10 09 09 07 3f 4-OHC6H4 09 13 10 11 11 09 3g 3-BrC6H4 14 11 15 13 08 07 3h 3-FC6H4 10 13 11 12 07 06 Streptomycin 17 18 22 20 --Griesofulvin ----18 20 a zone of inhibition was measured in mm. Staphylococcus aureus (S.a), Escherichia coli (E.c), Pseudomonas aeruginosa (P.a), Salmonella typhosa (S.t), Aspergillus niger (A.n), Candida albicans (C.a).

distillation and then it was poured into crushed ice and acidified with HCl. The solid separated was filtered and recrystallised from ethanol (Scheme-1). Similarly remaining compounds 3a-h was prepared by above method. The characterization data of these compounds is described in Table- 1 and 2.

medium and DMSO was used as solvent control for antimicrobial activity. Streptomycin and griseofulvin were used as standard for antibacterial and antifungal activities respectively.

CONCLUSION:
From the antimicrobial screening it was observed that all the compounds exhibited activity against all the organisms employed. Looking at the structure activity relationship, marked inhibition in bacteria was observed in the compounds bearing Ar = C6H5, 4-OCH3 C6H4, 4-OH C6H4, 3FC6H4, , 3-BrC6H4 (3a,3d,3f,3g,3h) substitutents where as other compounds showed moderate to good activity. Fungicidal screening data also revealed that compounds bearing Ar = C6H5, 2- NO2C6H4, 4-N(CH3)2 C6H4, 4-OCH3 C6H4, 4-OHC6H4 (3a,3b,3c,3d,3f) imparted maximum activity to the compounds, where as other compounds

ANTIMICROBIAL ACTIVITY:
The synthesised compounds (3a-3h) were screened for their in vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhosa and antifungal activity against Aspergillus niger, Candida albicans by measuring the zone of inhibition in mm. The antimicrobial activity was performed by cup plate method13-14 at concentration 500 g/mL and reported in Table-3. Nutrient agar was employed as culture

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Asian J. Research Chem. 1(2): Oct.-Dec. 2008. ,

showed moderate to good activity. As we consider all results obtained from antibacterial and antifungal tests together we can say that entire compounds tested are active towards bacteria and fungi.

REFERENCES:
1. 2. 3. 4. 5. 6. 7. Bigi F., Tetrahedron Lett., 2001, 42 , 5203. Handan A., Oznur A., Ayse K., Seher B., Gulten O., Indian. J. Chem., 2005, 44B, 585. Desai J.T., Desai C.K. and Desai K.R., J. Iran. Chem. Soc., 2008, 5(1), 67-73. Hogale M B, Dhore N P, Shelar A R and Pawar P K; Orient J. Chem., 1986, 2, 55; Chem. Abstr., 1987, 106, 32503a. Vamakawa T, Kagechika H, Kawachi E, Hashimoto Y and Shudo K; J. Med. Chem., 1990, 33,1430. Ahluwalia V K, Nayal L, Kaila N, Bala S, and Tahim A K; Indian J. Chem., 1987, 26B, 384. Bhatt A K, Bhamaria R P, Mrs. Patel M R, Bellare R A and Deliwala C V; Indian J. Chem., 1972, 10, 694; Chem. Abstr., 1973, 78,119650n. Mucherjee S, Kumar V, Prasad A K, Raj H G, Brakhe M E, Olsen C E, Jain S C and Parmar V P; Bio-org. Med.Chem., 2001, 9, 337. Indyah S A, Timmerman H, Samhoedi M, Sastronami D, SugiyantoH and Van Der Goot; Eur. J. Med. Chem., 2000, 35, 449. Chen M, Christensen S B, Zhai L, Rasmussen M H, Theander T G, Frokjaer S, Steffensen B, Davidson J and Kharazmi A; J. Infect. Dis., 1997, 176, 1327. Nielsen S F, Christensen S B, Cruciani G, Kharazmi A and Liljefors T; J. Med. Chem., 1998, 41, 4819. King, L.C; Hlavacek, R.J. Reaction of ketones with iodine and thiourea, J. Am. Chem. Soc., 1950,72, 3722. Shiradkar Mahendra, Kale Rajesh, Baviskar Bhushan and Dighe Rajendra ; Asian J. Chem., 2007, 19, 449. Indian Pharmacopoeia, Ministry of Health and Family Welfare, New Delhi, 1996 A-114.

ACKNOWLEDGEMENT:
The authors are thankful to Ms. D. S. Ghorpade, Head, Department of Pharmaceutical Biotechnology, Govt. College of Pharmacy, Amravati, 444 604 (M.S) India for biological screening.
Scheme 1. Synthesis of thiazolyl chalcones.

8. 9.
N

10.
NH2

11. 12.

CH3COCl

13. 14.

O N H C CH3

Ethanol

R-CHO NaOH

O N H C C H C H

3a-h

R = C6H5, 3-NO2C6H4, 4-N(CH3)2 C6H4, 4-OCH3 C6H4,3,4,5(OCH3)2 C6H4, 4-OHC6H4, 3-BrC6H4, 3-FC6H4

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