Synthesis and Anti-Inflammatory Activity of 2-Acetyl Thiophene
B. Ramesh* , S. V. Kulkarni and B. Someswara Rao
Dept. of Pharmaceutical Chemistry, Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur-572102. Karnataka
*Corresponding Author E-mail: rameshbbatta@gmail.com
ABSTRACT:
Some new chalcones have been synthesized by the condensation of 2-acetyl thiophene with various aromatic aldehydes in 40% alkali. The synthesized compounds were identified by spectral data and screened for anti-inflammatory activity. Some of these compounds showed moderate to considerable anti-inflammatory activity.
KEYWORDS: Chalcone, Synthesis, Anti-inflammatory activity.
INTRODUCTION:
Chalcones display interesting biological activities, including antimalarial1, anti-inflammatory2, cytotoxic3,4, anticancer5,6 and antimicrobial activities7,8. In the present study, some new chalcones (1-8) have been synthesized by the reaction of 2-acetyl thiophene with different aromatic aldehydes. The structures of the various synthesized compounds are assigned on the basis of elemental analyses, IR and 1H NMR spectral data. These compounds were also screened for their anti-inflammatory activity.
EXPERIMENTAL:
Melting points were determined on a capillary melting point apparatus and are uncorrected. 1H NMR spectra was recorded in the indicated solvent on Bruker WM 400 MHz spectrometer with TMS as internal standard. Infrared spectra were recorded in KBr on Perkin-Elmer AC-1 spectrophotometer. Microanalyses were performed on Carlo Erba EA-1108 element analyzer and were within the ± 0.5% of the theoretical values. Column chromatography was performed on silica gel (Merck, 60-120 mesh).
General procedure for the preparation of chalcones (1-8):
A mixture of 2-acetyl thiophene (0.01 mol) and appropriate aldehyde (0.01 mol) was stirred in ethanol (30 mL) and then an aqueous solution of KOH (40%, 15 mL) was added to it. The mixture was kept overnight at room temperature and then it was poured in crushed ice and acidified with HCl. The solid separated was filtered and crystallized from ethanol (Scheme 1). The characterization data of these compounds are described in Tables 1 and 2.
(1-8)
Scheme 1 : Synthesis of some new chalcones of 2-acetyl thiophene (1-8)
Anti-inflammatory activity:
Synthesized compounds (1-8) were tested for their anti-inflammatory activity. Male albino rats weighing between 200-250 g were used for the experiment. Carrageenan induced paw oedema method described by Singh and Ghosh9 was followed for the acute anti-inflammatory model and the results are presented in Table 3.
RESULTS AND DISCUSSION:
The screening results revealed that the compounds (1-8) exhibited moderate to considerable activity when compared with reference standard aceclofenac. The synthesized compounds showed anti-inflammatory activity in the range of 50-80% whereas standard drug showed 80-85% inhibition in paw edema. The results of anti-inflammatory activity indicated that compounds 3 and 4 showed maximum anti-inflammatory activity.
Table 1. Physical data of compounds (1-8)
|
Compound |
M.F. |
M.P (°C) |
Yield (%) |
Elemental analyses (%) |
|||||
|
C |
H |
O |
|||||||
|
Calculated |
Found |
Calculated |
Found |
Calculated |
Found |
||||
|
(1) (2) (3) (4) (5) (6) (7) (8) |
C13H9OSF C15H14O3S C13H9O3SN C13H9O3SN C12H9OSN C12H9OSN C11H8OSN C11H8OS2 |
82 86 162 240 180 210 134 86 |
81 71 83 76 82 32 34 86 |
67.24 65.69 60.23 60.23 66.97 66.97 65.02 60.00 |
67.2 65.66 60.16 60.18 66.84 66.84 65.00 59.90 |
3.87 5.10 3.47 3.47 4.18 4.18 3.94 3.66 |
3.84 5.10 3.46 3.44 4.16 4.14 3.92 3.63 |
6.89 17.51 18.53 18.53 7.44 7.44 7.88 7.27 |
6.89 17.51 18.53 18.53 7.44 7.42 7.76 7.27 |
Table 2. Spectral data of the compounds (1-8)
|
Compound |
IR (KBr, cm-1) |
1H NMR (CDCl3, ppm) |
|
(1) |
1720 (-C=O), 1650 (-CH=CH), 1120 (C-F), 650 (C-S). |
7.11 (2H, C-211 & 611-H) 7.19 (1H, C-41-H) 7.34 (1H, d, -CO-CH=) 7.635 (2H, m, C-311 & 511-H 7.685 (1H, d, C-31-H) 7.81 (1H, d, Ar-CH=) 7.85 (1H, d, C-51-H) |
|
(2) |
1641 (-C=O), 1579 (-CH=CH), 1141 (-OCH3), 715 (C-S). |
3.93 (3H, S, C-311-OCH3) 3.95 (3H, S, C-411-OCH3) 6.90 (1H, d, -CO-CH=) 7.14 (1H, d, C-611-H) 7.17 (1H, m, C-41-H) 7.25 (1H. d, C-511-H), 7.30 (1H, S, C-211-H) 7.66 (1H, d, C-31-H), 7.81 (1H, d, Ar-CH=) 7.86 (1H, d, C-51-H) |
|
(3) |
1519 (-C=O), 1593 (-CH=CH), 1337 (N=O), 660 (C-S). |
7.22 (1H, t,C-511-H) 7.52 (1H, d,-CO-CH=), 7.62 (1H,d,C-41-H) 7.74 (1H, d,C-411-H), 7.87 (1H,d,Ar-CH=) 7.91 (2H, m,C-611 & 31-H), 8.26 (1H,d,C-51-H) 8.51 (1H,S,C-211-H) |
|
(4) |
1710 (-C=O), 1653 (-CH=CH), 1510 (N=O), 650 (C-S). |
7.22 (1H, t, C-41-H) 7.51 (1H, d, -CO-CH=), 7.74 (1H,d,C-31-H) 7.79 (2H, d, C-211 & 611-H) 7.86 (1H, d, Ar-CH=) 7.89 (1H, d, C-51-H) 8.28 (2H, d, C-311 & 511-H) |
|
(5) |
1713 (-C=O), 1658 (-CH=CH), 643 (C-S), 1585 (C=N). |
5.41 (1H, d, -CO-CH=) 6.67 (1H, t, C-511-H) 6.92 (1H, t, C-41-H) 7.06 (2H, m, C-411 & 611-H) 7.15 (1H, d, Ar-CH=) 8.28 (2H, m, C-31 & 51-H) 8.61 (1H, S, C-211-H) |
|
Compound |
IR (KBr, cm-1) |
1H NMR (CDCl3, ppm) |
|
(6) |
1715 (-C=O), 1655 (-CH=CH), 1590 (C=N), 645 (C-S). |
5.37 (1H, d, -CO-CH=) 6.93 (1H, t, C-41-H) 7.07 (1H, d, Ar-CH=) 7.38 (1H, d, C-31-H) 7.62 (1H, d, C-51-H) 8.17 (2H, d, C-211 & 611-H) 8.34 (2H, d, C-311 & 511-H) |
|
(7) |
1598 (C=N), 1718 (-C=O), 1653 (-CH=CH), 648 (C-S). |
6.33 (1H, d, -CO-CH=) 7.03 (1H, d, Ar-H), 7.15 (1H, m, C-41-H) 7.63 (2H, t, C-31 & 51-H) 7.79 (3H, m, C-311, 411 & 511-H) |
|
(8) |
1700 (-C=O), 1650 (-CH=CH), 650 (C-S). |
7.09 (1H, m, C-411-H) 7.16 (1H, t, C-41-H) 7.21 (1H, d, -CO-CH=) 7.36 (1H, d, C-51-H) 7.42 (1H, d, C-511-H) 7.66 (1H, d, C-31-H) 7.84 (1H, d, C-311-H) 7.96 (1H, d, Ar-CH=) |
Table 3. Anti-inflammatory activity of the compounds (1-8)
|
Compound |
Percentage increase in paw thickness of various time intervals |
|||||
|
0.5 hr |
01 hr |
2 hr |
3 hr |
4 hr |
6 hr |
|
|
Standard Control 1 2 3 4 5 6 7 8 |
20.26± 0.64 - 13.41 ± 0.97 8.13 ± 0.08 14.47 ± 0.70 19.79 ± 0.62 21.79 ± 1.95 13.66 ± 1.02 11.36 ± 1.30 13.33 ± 0.55 |
23.95 ± 0.66 - 17.71 ± 0.83 23.25 ± 0.86 27.99 ± 4.54*** 31.07 ± 2.84* 22.71 ± 1.54 32.97 ± 3.65** 19.97 ± 5.37*** 21.34 ± 2.80 |
58.02 ± 1.54 - 41.16 ± 1.07 55.96 ± 3.06 36.67 ± 1.26 51.30 ± 3.52 51.88 ± 3.96** 55.30 ± 2.43* 53.62 ± 2.16 53.28 ± 2.41 |
67.93 ± 1.65 - 63.75 ± 1.97 75.84 ± 3.75** 64.11 ± 1.94 74.05 ± 2.77** 70.73 ± 3.27* 74.87 ± 3.66** 77.32 ± 4.27** 65.59 ± 2.05 |
97.09 ± 1.95 - 83.10 ± 4.82*** 86.34 ± 2.29* 78.33 ± 1.54 86.19 ± 1.26 86.29 ± 3.28* 83.75 ± 2.07* 83.75 ± 2.07* 80.66 ± 3.20 |
98.98 ± 1.98 - 84.64 ± 1.73 91.7 ± 2.97 86.24 ± 4.14** 83.16 ± 1.55 90.53 ± 1.54 88.01 ± 1.47 88.01 ± 1.47 86.71 ± 1.27 |
Control : 1% sodium CMC gel, standard : Aceclofenac standard and sample solution is 100 mg/ kg body weight, values are expressed as mean ± (n = 6)* = 2.28, ** = 3.75, *** = 4.35, P* < 0.05, P** < 0.01, P*** < 0.001 compared to control student t-test
ACKNOWLEDGEMENTS:
We are thankful to the Head, Sophisticated Instrumentation Facility, IISc, Bangalore for 1H NMR spectra and to Sipra Laboratories, Hyderabad for IR spectra.
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Received on 26.11.2009 Modified on 19.01.2010
Accepted on 18.02.2010 © AJRC All right reserved
Asian J. Research Chem. 3(2): April- June 2010; Page 332-334