Free Radical Scavenging Activity of Novel 5-Substituted Arylidene-3-Substituted-Benzyl-Thiazolidine-2, 4-Diones

 

Ankush Garg, Radhika Maheshwari, Pooja Chawla* and Shubhini A. Saraf

Faculty of Pharmacy, Babu Banarasi Das National Institute of Technology and Management, Dr. Akhilesh Das Nagar, Sector 1, Faizabad Road, Lucknow Pin 227105 (UP), India.

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

 

ABSTRACT:

A series of 5-substituted-arylidene-3-substituted-benzyl-thiazolidine-2, 4-dione derivatives were synthesized from thaizolidinedione and substituted benzyl chloride followed by the addition of substituted aromatic aldehydes. All the compounds 1(a)-1(e) and 2(a)-2(c) were screened for their in vitro antioxidant activity using DPPH method. The anisaldehyde based thiazolidinedione compounds 1(a) and 2(a) displayed good activity comparable to those of standard.

 

KEYWORDS: Thiazolidine-2, 4-dione, Heterocyclic compounds, Antioxidant activity

 


 

INTRODUCTION:

Thiazolidinedione (TZD) derivatives have been the subject of extensive research because of their deep involvement in the regulation of dierent physiological processes. TZDs such as troglitazone, pioglitazone, rosiglitazone and various substituted thiazolidinediones are potent reducer of plasma glucose level in vivo and in vitro1-3. Besides their anti-diabetic potency, these TZD derivatives have been shown to exert anti-inflammatory eects on vascular cells4-6. TZDs were also found to inhibit the production of inflammatory cytokines and the expression of inducible nitric oxide synthesis in monocytes/macrophages7. It has been shown that TZDs suppress the growth of several cancer cell lines including colon, breast, and prostate in vivo and in vitro8-9. Differently substituted thiazolidinedione moiety has been found to have other interesting activities such as aldose reductase inhibition10-12 and antimicrobial activity13-15. Antioxidants are known to be interceptors of peroxy radicals and singlet oxygen that therefore inhibit lipid peroxidation which has been implicated in the alterations of glucose transport and microangiopathic disease in diabetes. The literature survey reveals that thiazolidinedione based drugs exhibit antioxidant activity16. So in present work, an attempt has been made to synthesize analogues of 5-substituted arylidene-3-substituted-benzyl-thiazolidine-2, 4-dione expecting their enhanced antioxidant activity.

 

Chemistry:

5-substituted-arylidene-3-substituted-benzyl-thiazolidine-2, 4-dione (3) was prepared by a nucleophilic addition of 3-substituted-benzyl-thiazolidine-2, 4-dione (2) with selected various substituted aromatic aldehydes according to Bradsher et al17. Synthetic pathway is shown in Fig.1. Thiazolidinedione (1) was refluxed with substituted benzyl chloride as 4-nitrobenzyl bromide or 4-chloro benzyl chloride for about 18 hours18. The substituted 3-benzyl-thiazolidine-2, 4-dione (2) was obtained in this way.

 

Fig.1. Synthetic pathway of 5- arylidene-3-benzyl-thiazolidine-2, 4-dione

Antioxidant activity:

The synthesized compounds (1a-1e and 2a-2c) were tested for in vitro antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The free radical scavenging potentialities of the compounds were measured in terms of hydrogen donating or radical scavenging ability after adding 1 ml methanolic solution of DPPH (0.1 mM) to 3 ml of sample solution in methanol at different concentrations (10-40 µg/ml). The test compounds react with DPPH and convert it to 1, 1-diphenyl-2-picrylhydrazine. The degree of decolourization indicates the scavenging potentialities of the antioxidant drug. The change in absorbance produced at 517 nm has been used as a measure of antioxidant activity. Reduction of the DPPH radicals can be observed by the decrease in absorbance at 517 nm. The IC50 is the 50% inhibition concentration and were calculated from regression lines. Among the tested compounds 1(a), 1(b), 1(d) and 2(a) were found to have potent free radical scavenging activity than ascorbic acid (Table 1). Scavenging activity is determined by formula:

 

                        Control absorbance – Test absorbance

% Reduction = ---------------------------------------------- x 100

                                       Control absorbance

 

Fig.1. Graphical representation of % DPPH radical scavenging activity of compounds 1a-1e and ascorbic acid

 

Fig.2. Graphical representation of % DPPH radical scavenging activity of compounds 2a-2c and ascorbic acid

 

RESULTS AND DISCUSSION:

All the synthesized compounds were found to scavenge DPPH radical significantly in a concentration dependent manner. Compounds 1(a), 1(b), 1(c), 1(d), 2(a), 2(b), 2(c) showed appreciable free radical scavenging activity. The activity showed by the anisaldehyde based compounds 1(a) and 2(a) was comparable to that of ascorbic acid. The strong activity exhibited by 1(b) may be attributed to the presence of the free OH group on the aryl moiety of 5-arylidene-2, 4-thiazolidinediones, which can donate hydrogen atoms. The presence of free hydroxyl group in the aryl moiety is one of the factors in determining the DPPH scavenging activity of the compound is also described by Tominaga et al.19 where protection of the free hydroxyl group drastically reduced the DPPH scavenging activity.

 

CONCLUSION:

The new series of 5-substituted-arylidene-3-substituted-benzyl-thiazolidine-2, 4-diones have shown promising antioxidant activity at different concentrations 10 μg/ml, 20 μg/ml, 30 μg/ml, and 40 μg/ml. The anisaldehyde based thiazolidinedione compounds 1(a) and 2(a) displayed antioxidant activity comparable to ascorbic acid at the conc. of 40 μg/ml.

 

Experimental Protocols:

5-substituted-arylidene-3-substituted benzyl-thiazo lidine-2, 4-diones (1a-1e) and (2a-2c): General procedure.

To a solution containing 0.01 mole (0.143 g) of benzaldehyde and 0.01 mole (0.25 g) of 3-substituted-benzyl-thiazolidine-2, 4-dione in 1.0 ml of hot acetic acid, 0.01 mole (0.338 g) of fused sodium acetate was added and the mixture refluxed for 1.5 hr. The product was obtained by pouring the mixture into water followed by recrystallizing the resulting solid from ethanol.

 

1.      5-(4-Methoxy-benzylidene)-3-(4-nitro-benzyl)-thiazolidine-2, 4-dione (1a)

C18O5N2SH14, yield: 83.2%, M.P. 180-183˚C. TLC ethanol: chloroform (9:1) Rf: 0.62. IR cm-1 (KBr):  1595, 1670, 1650, 3050, 1550, 1020. MS (FAB) m/z: 370 (M+), 371 (M++1, 100%).

 

2.      5-(4-Hydroxy-3-methoxy-benzylidene)-3-(4-nitro-benzyl)-thiazolidine-2,4-dione (1b)

C18O6N2SH14, yield: 78.5%, M.P. 195-200˚C. TLC ethanol: chloroform (9:1) Rf: 0.55. IR cm-1 (KBr):  1540, 1520, 3045, 1675, 1720, 3000, 1100, 3320. MS (FAB) m/z: 386 (M+), 386 (M+, 100%).

 

3.      5-(4-Chloro-benzylidene)-3-(4-nitro-benzyl)-thiazolidine-2, 4-dione (1c)

C17O4N2SClH11, yield: 85.7%, M.P. 205-210˚C. TLC ethanol: chloroform (9:1) Rf: 0.72. IR cm-1 (KBr):  1522 and 1379, 1605, 976 and 886, 3416, 2946, 703 and 663. MS (FAB) m/z: 374 (M+), 375 (M++1, 100%).

 


Table1. Inhibition of DPPH radical by synthesized compounds

S.NO.

Compound Control

Absorbance at 517 nm

IC50

 

10 μg/ml

20 μg/ml

30 μg/ml

40 μg/ml

1

1(a)

51.16

60.21

67.35

77.98

17.10

2

1(b)

44.25

52.32

60.91

75.65

8.22

3

1(c)

18.15

26.37

35.64

42.36

2.597

4

1(d)

54.22

65.55

65.97

70.99

48.77

5

1(e)

1.1

0.9

1.3

1.6

3.78

6

2(a)

50.65

77.31

79.92

86.27

22.07

7

2(b)

20.87

25.82

33.33

44.54

61.10

8

2(c)

13.7

22.67

25.27

36.26

49.06

9

Ascorbic acid

61.53

68.13

75.27

82.96

5.6

 

 


4.      5-(3,4Dimethoxy-benzylidene)-3-(4-nitro-benzyl)-thiazolidine-2, 4-dione (1d)

C19O6N2SH16, yield: 81.3%, M.P. 172-179˚C. TLC ethanol: chloroform (9:1) Rf: 0.50. IR cm-1 (KBr):  1575, 1675 and 1480, 3060, 1575, 1740, 3010, 1150. MS (FAB) m/z: 400 (M+), 401 (M++1, 100%).

 

5.      5-(Furfural-benzylidene)-3-(4-nitro-benzyl)-thiazolidine-2, 4-dione (1e)

C15O5N2SH10, yield: 74.4%, M.P. 165-170˚C. TLC ethanol: chloroform (9:1) Rf: 0.45. IR cm-1 (KBr):  1390 and 1535, 1570, 3080, 1690, 1630, 700, 3110. MS (FAB) m/z: 330 (M+), 331 (M++1, 100%).

 

6.      5-(4-Methoxy-benzylidene)-3-(4-chloro-benzyl)-thiazolidine-2, 4-dione (2a)

C18O3NSClH14, yield: 80.3%, M.P. 193-198˚C. TLC ethanol: chloroform (9:1) Rf: 0.52. IR cm-1 (KBr):  763, 1608, 1381, 1686, 1753, 669, 3022, 1150. MS (FAB) m/z: 359 (M+), 360 (M++1, 100%).

 

7.      5-(4-Chloro-benzylidene)-3-(4-chloro-benzyl)-thiazolidine-2, 4-dione (2b)

C17O2NSCl2H11, yield: 82.1%, M.P. 185-190˚C. TLC ethanol: chloroform (9:1) Rf: 0.48. IR cm-1 (KBr):  603 and 537, 3069, 667, 1676, 1751. MS (FAB) m/z: 363 (M+), 364 (M++1, 100%).

 

8.      5-(2-Chloro-benzylidene)-3-(4-chloro-benzyl)-thiazolidine-2, 4-dione (2c)

C17O2NSCl2H11, yield: 75.9%, M.P. 168-175˚C. TLC ethanol: chloroform (9:1) Rf: 0.66. IR cm-1 (KBr):  763, 1603 and 1381, 1686, 1753, 669, 3021. MS (FAB) m/z: 363 (M+), 364 (M++1, 100%).

 

ACKNOWLEDGEMENT:

The authors are thankful to Faculty of Pharmacy, B.B.D.N.I.T.M., Lucknow for financial assistance. The authors are also thankful to CDRI, Lucknow for spectral analysis.

 

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Received on 18.12.2009        Modified on 25.01.2010

Accepted on 17.02.2010        © AJRC All right reserved

Asian J. Research Chem. 3(3): July- Sept.  2010; Page 528-530