SYNTHESIS, CHARACTERIZATION AND STUDY OF ANTIMICROBIAL ACTIVITY OF 2-HYDROXY 3-NITRO-5-METHYL-N-(SUBSTITUTED PHENYL) CHALCONE IMINESHTML Full Text
SYNTHESIS, CHARACTERIZATION AND STUDY OF ANTIMICROBIAL ACTIVITY OF 2-HYDROXY 3-NITRO-5-METHYL-N-(SUBSTITUTED PHENYL) cHALCONE IMINES
S. B. Borul *1 and S. V. Agarkar2
Department of Chemistry 1, Late Ku. Durga K. Banmeru Science College, Lonar, Dist- Buldana (M.S.) India
Anuradha Engineering College 2, Chikhli, Dist- Buldana (M.S.) India
ABSTRACT: Chalcones and its derivatives show various biological activities. The present study deals with the synthesis of series of 2-hydroxy-3-nitro-5-methyl–N-substituted phenyl chalcone imines from 2-hydroxy-3-nitro-5-methylphenyl chalcone and different substituted aromatic animes in ethanol in presence of 2, 3 drops of Conc. H2SO4. Structures of synthesized compounds have been established by spectral (IR, NMR, etc.) and elemental analysis. In the present communication we report the synthesis substituted chalcone imines and its antimicrobial activity against pathogenic bacteria and fungi. The sensitivity carried out by disc diffusion method displayed significant antimicrobial activity
Chalcone imines, antibacterial activity and inhibition zone
INTRODUCTION: Chalcones and its derivatives show various biological activities. Chalcones are medicinally important class of compounds. It is also used as main intermediate for synthesis of heterocyclic compounds like pyrazolines1, isoxazolines 2, flavonone3, pyrimidines4, etc. They have been reported to possess biological activities such as antioxidant5, antimalarial,6 anlgesic,7 antiinflammatory,8 anticancer 9 , insecticidal10-11, antibacterial activity12-13, fungicidal14-15, activities. Chalcone imines are the phenolic Schiff bases, the present study deals with the synthesis of series of 2-hydroxy-3-nitro-5-methyl–N-substituted phenyl chalcone imines from 2-hydroxy-3-nitro-5-methylphenyl chalcone and different substituted aromatic animes.
chalcone imines from chalcone and different substituted aromatic animes. Structures of synthesized compounds have been established by spectral (IR, NMR, etc.) and elemental analysis. The synthesized chalcone imines were screened for their antimicrobial activity against bacteria like Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi and antifungal activity against Aspergillus niger, Aspergillus fumigates, Rhizopus and Candida albicans carried out by disc diffusion method displayed significant antimicrobial activity.
Synthesis of 1-(2'-hydroxy-3'-nitro-5'-methyl phenyl)-3-phenyl-2-propen-1-one(Chalcone) (Reaction Scheme1):
A mixture of equimolar quantities of 2'-hydroxy-3'-nitro-5'-methyl acetophenone (0.01 moles) and benzaldehyde (0.01 moles) were dissolved in ethanol and 40 % KOH was added in portions at 100C with stirring. The reaction flask was corked and kept at room temperature for 12hrs (overnight). The contents of the flask were then acidified by dilute hydrochloric acid and poured over ice-cold water. Solid obtained was filtered, washed with water and crystallized from proper solvents.
Yield: 75%; colour: pale yellow crystalline solid; Melting point: 125oC; Molecular formula: C16H13O4N; Molecular weight: 283.
IR (KBr, cm-1):3523(O-H), 1667(C=O), 1580 and 1450 (C=C, phenyl), 1614 (C=C, ethylenic). 1H-NMR (CDCl3 on Bruker Avance II 400 NMR Spectrometer using TMS as internal standard): 12.10 (s, 1H, -OH), 8.12(d, 1H, Ar-CH), 7.52(1H, Ar-CH), 6.99-6.93(m, 5H, Ar-H).
Synthesis of 2-hydroxy-3-nitro-5-methyl–N-substituted phenyl chalcone imines (2a-j) (Reaction Scheme 2):
The equimolar amount of 2-hydroxy-3-nitro-5-methylphenyl chalcne (0.01moles) and substituted aromatic amines (0.01moles) was dissolved in ethanol (20ml) and add 2, 3 drops of Conc. H2SO4 and refluxed for 4 hrs. Completion of reaction is monitor by TLC. After completion of reaction cool the reaction mixture dilute with ice cold water separated solid 2-hydroxy-3-nitro-5-methyl–N-substituted phenyl chalcone imines was obtained, these are filtered and purified.
Antibacterial activity of synthesized compounds (2a-j):
Antibacterial test sample solution was prepared by dissolving 100mg of sample in 1ml of DMF. All the synthesized compounds (2a-j) were tested by disc diffusion method against the bacteria as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi. The antibacterial activities of all compounds are compared against Amplicilline as a standard drug as shown in Table 2.
Antifungal activity synthesized compounds (2a-j):
The antifungal activity of all synthesized compounds was studies at 1000ppm concentration in vitro. Plant pathogenic organisms were Aspergillus niger, Aspergillus fumigates, Rhizopus and Candida albicans. The antifungal activity of all the compounds was measured on each of these plants pathogenic strains on potato dextrose agar (PDA). 5-6 day old cultures were employed. The inhibition for fungi was calculated after five days using the formula as Percentage of inhibition = 100(x-y) / x, where, x= area of colony in control plate. And y= area of colony in test plate as shown in Table 3.
Reaction Scheme 1:
Reaction Scheme 2:
TABLE 1: THE OTHER CHALCONE IMINES PREPARED ARE TABULATED
|Sr. No.||Compounds||R1||R2||R3||M.P. (0C)||Yield (%)|
TABLE 2: ANTIBACTERIAL ACTIVITY OF CHALCONEIMINES (2a-j)
|Compounds||Escherichia coli||Staphylococcus aureus||Pseudomonas aeruginosa||Salmonella typhi|
Zone of inhibition measure in mm
TABLE 3: ANTIFUNGAL ACTIVITY OF CHALCONEIMINES (2a-j)
|Compounds||Aspergillus niger||Aspergillus fumigates||Candida albicans||Rhizopus|
Zone of inhibition measure in mm
RESULT AND DISCUSSION
In present study new 2-hydroxy-3-nitro-5-methyl–N-substituted phenyl chalcone imines have been synthesized by the reaction of 2-hydroxy-3-nitro-5-methylphenyl chalcone and aromatic substituted amines at reflux using ethanol as solvent in presence of conc. H2SO4 in 52-78% yield. Structures of all these synthesized compounds were established on the basis of spectral data (IR, NMR) and elemental analysis.
All the compounds (2a-j) were tested for their antimicrobial activity against the bacteria Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi and Aspergillus niger, Aspergillus fumigates, Rhizopus, Candida albicans. The results were compared with the standard antibacterial drug Amplicilline and standard antifungal drug Greseofulvin. The Zones of inhibition for antibacterial activity were summarized in Table 2 and for antifungal activity were summarized in Table 3. Some compounds as 2g, 2h, 2i, and 2j shows higher activity against the microorganism. While other shows moderate activity against the microorganism.
CONCLUSION: In present study new 2-hydroxy-3-nitro-5-methyl–N-substituted phenyl chalcone imines have been synthesized with percentage yield range 52-78%. Structures of all these synthesized compounds were established on the basis of spectral data (IR, NMR) and elemental analysis. From the antimicrobial activity it has been interesting to note that the chalconeimines were more active against the microorganism.
- Ji-Tai Li, Xiao-Hui Zhang and Zhi-Ping Lin, Beilstein Journal of Organic Chemistry 2007; 3- 13.
- Desai JT, Desai CK, Desai KR, J. Iran. Chem. Soc. 2008; 5, 1, 67-73.
- Ragab FA, Hassan GS, Yossef HA, Hashem HA, European Journal of Medicinal Chemistry 2007; 42, 1117-1127.
- Bamnela R, Shrivastava SP, E-Journal of Chem. 2010;7, 3, 935-941.
- Miranda CL, Aponso GLM, Stevens JF, et al., J Agric. Food Chem, 2000; 48, 3876.
- Liu M, Wilairat P, Go LM, J. Med. Chem; 2001, 44, 4443.
- Viana GS, Bandeira MA, Matos F, J. Phytomedicine 2003; 10, 189.
- Rangari V, Gupta VN, Atal CK. Indian J Pharm Sci.1990; 52, 158–60.
- Francesco E, Salvatore G, Luigi M, Massimo C, Phytochem 2007; 68, 939.
- Nissan Chemical Industries Ltd., Japan Kokai Tokkyo Koho Japan 1983; 58, 08, 035, Chem.Abstr., 1983, 98, 178947a.
- Seele R. et al. Eur. Pat. Appl. Ep.1989; 337, 198 (Cl C07D, 249/08); Chem. Abstr.1990; 113, 178990s.
- Bowden K, Dal PA, Shah CK, J. Chem. Res. Synop. 1990; 12, 2801; Chem. Abstr.1991; 114, 160570m.
- Inamori Y. et al. Chem. Pharm. Bull.1991; 39(6), 1604; Chem. Abstr.1991; 115, 105547c.
- Gaurav VM, Ingle DB, Indian J. Chem.1986; 25B, 868; Chem. Abstr. 1987; 107, 39321h.
- Pedersen AK, Fitz Gerald GA, J. Pharm. Sci.,1985, 74(2), 188 ; Chem. Abstr.1985; 103, 87592m.
- Abonia R, Cuervo P, Castillo J, et. al, Tetrahedron Letters 2008;49, 5028-5031.
- Bamnela R, Shrivastava SP, E-Journal of Chem. 2010; 7, 3, 935-94.
- Kolundžija B, Marković V, Stanojković T, Joksović L, Matić I, Todorović N, Nikolić M, Joksović MD, Novel anthraquinone based chalcone analogues containing an imine fragment: synthesis, cytotoxicity and anti-angiogenic activity. Bioorganic & Medicinal Chemistry Letters 2014; 1; 24(1):65-71.
- Shubhangi Patil, Prashant Utale, Suresh Gholse, Sachin Pande, Sumer Thakur Synthesis, characterization and antimicrobial activity of 2-hydroxy-5-bromo-N-(substituted phenyl) chalconeimine. Asian Journal of Biochemical and Pharmaceutical Research 2013 ; 2,3
- Rane, R.A.; Telekar, V.N "Synthesis and] evaluation of novel chloropyrrole molecules designed by molecular hybridization of common pharmacophores as potential antimicrobial agents" Med. Chem. Lett, 2010; 20, 5681-5685.
- Kumar, D., Kumar, N.M, Akamatsu, K. Kusaka, E., Harada, "Synthesis and biological evaluation of indolyl chalcones as antitumor agents". Boorg. Med. Chem. Lett.2010; 20, 3916-3919.
- Urbain C. Kasséhin, Fernand A. Gbaguidi, Christopher R. McCurdy and Jacques H. Poupaert, Synthesis of antitrypanosomal thiosemicarbazones using anthranilic acid as an innovative Green nucleophilic catalyst. Journal of Chemical and Pharmaceutical Research 2014; 6(10):607-612.
- G. Patila, P. S. Utaleb, S. B. Gholsea, S. D. Thakurc, S. V. Pandea, Synthesis, characterization and antimicrobial activity of 6-bromo-4-methoxy-4-(substituted phenyl) iminoflavone, Journal of Chemical and Pharmaceutical Research2012, 4,1:501-507.
- Sida Shen, Pham Van Khang, Yijia Chen, Min Lei and Lihong Hua, Catalyst-free one-pot synthesis of isoindolin-1-imine derivatives via three-component reaction. ARKIVOC; 2013 (iii) 413-423.
- More, V. Mola, A. D. Perillo, M. Caprariis, P. D. Filosa, R. Peduto, A. Massa, A. Synthesis; 2011, 3027.
- Zhang, H., Maryanoff, B., White, K., Yabut, S. C., Ye, H., Abstr.; 2011, 154, 557419.
How to cite this article:
Borul SB and Agarkar SV: Synthesis, Characterization and Study of Antimicrobial Activity of 2-Hydroxy 3-Nitro-5-Methyl-N-(Substituted Phenyl) Chalcone Imines. Int J Pharm Sci Res 2015; 6(8): 3424-27.doi: 10.13040/IJPSR.0975-8232.6(8).3424-27
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
S. B. Borul * and S. V. Agarkar
Department of Chemistry, Late Ku. Durga K. Banmeru Science College, Lonar, Dist- Buldana (M.S.) India
07 December, 2014
08 February, 2015
26 April, 2015
01 August, 2015