EHOOPrAHH^ECKAa XHMH3, 2013, moM 39, № 3, c. 353-357
Eco-Friendly Synthesis and in vitro Antibacterial Activities of Some Novel Chalcones
© 2013 Salman A. Khan", *, Abdullah M. Asiri", b, Khalid A. Alamry", Samy A. El-Daly", Mohie A. M. Zayed"
aDepartment of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia bCenter of Excellence for Advanced Materials Research, King Abdulaziz University, P.O. Box 80203,
Jeddah 21589, Saudi Arabia Received September 18, 2012; in final form December 7, 2012
Chalcone derivatives have been synthesized by reaction of 1-(2,5-dimethyl-furan-3-yl)-ethanone with corresponding active aldehyde in ethanolic NaOH in microwave oven. The structure of these compounds was established by elemental analysis, IR, 1H-NMR, 13C-NMR, and EI-MS spectral analysis. The anti-bacterial activity of these compounds was first tested in vitro by the disc diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined with the reference of standard drug Chloramphenicol. The results showed that pyrazol containing chalcone (compound 8) inhibited both types of bacteria (Gram-positive and Gram-negative) better than chloramphenicol.
Keywords: chalcones, anti-bacterial activity, Chloramphenicol.
DOI: 10.7868/S013234231303007X
INTRODUCTION
The rapid rise in the pathogen infections such as food poisoning, rheumatic, salmonellosis, and diarrhea have become the topic of concern for many researchers. These serious health problems are caused by Staphylococcus aureus, Staphylococcus pyogenes, Salmonella ty-phimurium, and Escherichia coli [1]. Amoxicillin, norfloxacin, and ciprofloxacin are the principal drugs of choice in the treatment of these bacterial infections. These drugs are found to be effective against intestinal and extraintestinal wall infection, but there are various side effects such as nausea, metallic taste, dizziness, hypertension, etc. associated with these drugs. The rise in the bacterial resistance to these drugs has encouraged the continuing search for new classes of compounds with novel modes of antibacterial activity [2]. Chalcones (trans-1,3-diphenyl-2-propen-1-one) are carbo-nyl systems; they consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon a, P-unsaturated system [3]. Chalcones have been reported to possess many useful properties, including anti-inflammatory, antimicrobial, antifungal, antioxidant, cytotoxic, antitumor, and anticancer activities [4—9]. Recent developments in anti-bacterial agents involve structural modification of chalcones to improve their bioavailability and study the role ofvarious substit-uents on aryl or heteroaryl rings [10]. Introduction of a heterocyclic ring into chalcones dramatically increases
* Corresponding author: e-mail: sahmad_phd@yahoo.co.in.
the diversity of certain biological properties such as antibacterial, antiviral, and antiamoebic activities [11]. Various synthetic methods have been reported so far, such as refluxing in an organic solvent [12], solvent-free solid-phase reaction [13], ultrasonication [14], and microwave radiation [15]. Microwave radiation has attracted the attention of medicinal chemists due to its unique advantages. In view of these findings, herein we describe a simple and convenient method for the synthesis of chalcones under microwave irradiation in solvent free environment, with improved yields and short reaction time.
RESULTS AND DISCUSSION
Chemistry
Chalcone derivatives were synthesized by the reaction of1-(2,5-dimethyl-furan-3-yl)-ethanone and corresponding active aldehyde (Scheme and Table 1). The purified products was characterized by EI-MS m/z values (rel. int. %), FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. The IR spectra of compounds (1—8) show the characteristic band: the v(C=O) peak of Act-furan observed at 1668 cm-1 shifts to a lower frequency of1636-1655 cm-1 in chalcones. This is due to the conjugation of the n-electrons of the benzene moiety with those of the ethylene moiety in the enone linkage. 1H NMR spectra is a proved diagnostic tool for the positional elucidation of the proton. Assignments of the signals are based on chemical shift and intensity pattern.
354 SALMAN A. KHAN et al.
Table 1. Physicochemical data on the synthesized compounds (1—8)
Compound no. Ar^ Molecular formula Crystallization % Yield Reaction Time (microwave)
1 OH (У C15H14O3 CHCl3 87.8 35 s
2 XT C16H16O3 CH2Cl2 89.5 42 s
3 MeO^Ç^ OMe C17H18O4 CH2Cl2 87.8 46 s
4 OMe хУ MeO^Y OMe C18H20O5 CHCl3 88.5 52 s
5 1 C17H19NO2 CHCl3 86.8 45 s
6 O^N^ 1_ C23H21NO2 CH2Cl2 87.5 42 s
7 OMe (У C16H16O3 CHCl3 90.0 40 s
8 HîW il N CH3 ô C20H20N2O2 CHCl3 88.6 46 s
The XH NMR spectra of all the compounds (1—8) measured at room temperature show two doublets at 7.60— 8.01 ppm (J = 15.6) and 6.07-7.25 ppm (J = 15.6 Hz)
indicating that the ethylene moiety in the enone linkage is in the trans-configuration which confirms the formation of chalcones.
БИООРГАНИЧЕСКАЯ ХИМИЯ том 39 № 3 2013
ECO-FRIENDLY SYNTHESIS AND IN VITRO ANTIBACTERIAL ACTIVITIES 355
Table 2. Antibacterial activity of chalcones measured by the halo zone (mm) test; positive control, chloramphenicol (Chlor.) and negative control, DMSO
Compounds Corresponding effect on microorganisms
S. aureus S. pyogenes S. typhimurium E. coli
1 9.8 ± 0.3 9.6 ± 0.2 9.0 ± 0.3 9.2 ± 0.4
2 10.2 ± 0.2 11.2 ± 0.4 10.8 ± 0.3 11.6 ± 0.2
3 11.2 ± 0.3 11.4 ± 0.4 10.6 ± 0.4 11.4 ± 0.4
4 9.6 ± 0.3 9.2 ± 0.5 11.9 ± 0.4 12.2 ± 0.1
5 10.6 ± 0.2 12.2 ± 0.3 11.8 ± 0.4 12.2 ± 0.4
6 10.8 ± 0.4 10.6 ± 0.4 12.8 ± 0.5 12.6 ± 0.5
7 11.8 ± 0.3 12.2 ± 0.5 12.6 ± 0.2 13.6 ± 0.5
8 18.0 ± 0.4 18.2 ± 0.5 19.4 ± 0.4 21.2 ± 0.5
Chlor. 17.0 ± 0.5 18.2 ± 0.4 17.2 ± 0.8 20.0 ± 0.2
DMSO - - - -
Table 3. Minimum inhibition concentration (MIC) of chalcones (1—8), positive control, chloramphenicol
MIC (^g mL Compound
1 2 3 4 5 6 7 8 control
S. aureus 512 512 256 512 256 128 128 16 32
S. pyogenes 512 256 128 512 128 128 64 32 32
S. typhimurium 512 512 256 128 128 64 64 16 32
E. coli 512 256 128 128 128 64 64 16 32
13C NMR (CDCl3) spectra of chalcones (1-8) were recorded in CDCl3 and the spectra are in good agreement with the theoretic structure 13C NMR spectra proposed for all compounds.
Characteristic peaks were observed in the EI mass spectra of compounds 1-8, which followed common molecular ion peak and fragmentation patterns.
Antimicrobial activity
The compounds (1-8) were tested for their antibacterial activities by disc-diffusion method [16]. The Gram-positive bacteria and Gram-negative bacteria utilized in this study included S. aureus, S. pyogenes, S. typhimurium, and E. coli. The results (see Tables 2 and 3) show that the nitrogen-containing heterocyclic chalcones exhibited increased antibacterial activity. Among the entire eight compounds, pyrazol-contain-
ing chalcone (8) exerted antibacterial activity against S. aureus and S. pyogenes higher than that of the reference drug chloramphenicol.
EXPERIMENTAL
General method for the synthesis of chalcones
To a solution of1-(2,5-dimethyl-furan-3-yl)-etha-none (0.34 g, 2.5 mmol) and corresponding active aldehyde (2.5 mmol) in dry ethanol (20 mL) taken in a beaker (100 mL), a catalytic quantity of sodium hydroxide (0.05 g, 1.25 mmol) was added and the reaction mixture was heated inside a microwave oven for 35—52 s (at 210 W, i.e. ~30% microwave power) [15]. The reactions were monitored through TLC using solvent system ethyl acetate : benzene (2 : 8), When the reaction was complete the reaction mixture was cooled
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in an ice bath and the product thus formed was filtered, washed with ethanol followed by washing with water till the washings were neutral and recrystallized from distilled ethanol and chloroform.
(2E)-1-(2,5-dimethylfuran-3-yl)-3-(2-hydroxyphenyl)prop-2-en-1-one (1)
Orange solid: m.p. 137°C; EI-MS m/z (rel. int. %): 244 (62) [M + 1]+; IR (KBr) vmax cm-1: 3134 (OH), 2914 (C-H), 1642 (C=O), 1554 (C=C); 1H NMR (600 MHz, CDCl3) 8: 9.74 (s, OH), 7.73 (d, C=CH, J= 15.6 Hz), 7.02 (d, CO=CH, J = 15.6 Hz), 7.516.67 (m, 6.33 (s, CH), 2.60 (s, -CH3), 2.28 (s, -CH3); 13C NMR (CDCl3) 8: 186.23, 157.04, 151.80, 149.70, 143.68, 130.17, 122.80, 122.62, 119.11, 111.78, 105.81, 40.15, 40.15, 14.41, 40.30; Anal. calc. for C15H14O3: C, 74.36, H, 5.82. Found: C, 74.32, H, 5.78.
(2E)-1-(2,5-dimethylfuran-3-yl)-3-(4-methoxyphenyl)prop-2-en-1-one (2)
Light-yellow solid: m.p. 85.5°C; EI-MS m/z (rel. int. %): 258 (65) [M + 1]+; IR (KBr) vmax cm-1: 2922 (C-H), 1654 (C=O), 1564 (C=C); 1H NMR (600 MHz CDCl3) 8: 7.70 (d, C=CH, J = 15.6 Hz), 7.56 (d, CH, J = 8.4 Hz), 6.92 (d, CH, J = 1.8 Hz), 6.32 (s, CH), 6.07 (d, CO=CH, J = 15.6 Hz), 6.34 (s, CH), 3.84 (s, -OCH3), 3.75 (s, -OCH3), 2.60 (s, -CH3), 2.23 (s, -CH3); 13C NMR (CDCl3) 8: 186.01, 161.40, 151.61, 149.92, 142.57, 130.03, 127.61, 122.56, 121.86, 114.31, 105.70, 55.38, 14.46, 13.27; Anal. calc. for C16H16O3: C, 74.98, H, 6.29. Found: C, 74.92, H, 6.25.
(2E)-3-(3,4-dimethoxyphenyl)-1-(2,5-dimethylfuran-3-yl)prop-2-en-1-one (3)
Yellow solid: m.p. 140°C; EI-MS m/z (rel. int. %): 288 (75) [M + 1]+; IR (KBr) vmax cm-1: 3122 (C-H), 2961 (C-H), 1654 (C=O), 1587 (C=C); 1H NMR (600 MHz, CDCl3) 8: 7.60 (d, C=CH, J = 15.6 Hz), 7.20 (d, CH, J = 1.2 Hz), 7.19 (d, CH, J = 1.8 Hz), 7.11 (s, CH), 6.89 (d, CO=CH, J = 15.6 Hz), 6.34 (s, CH), 2.61 (s, -OCH3), 2.53 (s, -OCH3), 2.29 (s, -CH3), 2.25 (s, -CH3); 13C NMR (CDCl3) 8: 186.01, 157.69, 151.12, 149.95, 149.12, 142.91, 127.87, 122.89, 122.15, 111.02, 109.91, 105.69, 55.98, 55.92, 14.45, 13.29; Anal. calc. for C17H18O4: C, 71.31, H, 6.39. Found: C, 71.27, H, 6.35.
(2E)-1-(2,5-dimethylfuran-3-yl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one (4)
Light-yellow solid: m.p. 128°C; EI-MS m/z (rel. int. %): 318 (68) [M + 1]+; IR (KBr) vmax
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