Synthesis, Characterisation and CNS Activity of

1,3-bis(2-hydroxybenzylidene)thiourea and 2-(2- hydroxybenzylidene amino) Acetic acid Schiff bases

 

Valli G.¹*, Ramu K.¹, Mareeswari P.¹ and Thanga Thirupathi A.²

¹Department of Chemistry, SFR College for Women, Sivakasi.

²Department of  Pharmacology, SB College of Pharmacy, Anaikuttam, Sivakasi.

 

ABSTRACT:

 

 

INTRODUCTION:

Various literature reviews the importance of Schiff bases. The Schiff bases play a vital role and find its use in analytical chemistry, agriculture, dyes and polymer industries besides their utility as model systems in the field of bio-inorganic chemistry. Schiff bases serve as useful gravimetric, colorimetric agent as well as anti-coagulant agent. The oxygen carrying property and electron transfer reactions of various schiff bases have been reported.

 

Schiff bases are capable of forming coordinate bonds with many of metal ions through both azomethine group and phenolic group or via its azomethine or phenolic groups^1-15.

 

A large number of Schiff bases and their complexes   have shown   significant interest and attention because of their biological activity including anti-tumor, antibacterial, fungicidal and anti-carcinogenic properties^3-8 and catalytic activity^8-15.

 

 Schiff base of salicylaldehyde-glycine has been show radio protective, antibacterial, fungi static^16,17, DNA cleavable¹⁸, antipyretic, and diabetic activities¹⁹.

 

In view of these above biological importance of Schiff bases, we plan to synthesis 1,3-bis(2-hydroxybenzylidene)thiourea and 2-(2- hydroxybenzylidene amino) acetic acid Schiff bases by standard procedure. The present work focus on the synthesis of the Schiff bases from salicylaldehyde by condensing with thiourea and glycine in ethanol at 50-60°C for two hours. The synthesized compounds have been characterized on the basis of their melting point and IR spectral data and CNS depressant activity were studied.

 

MATERIALS AND METHODS:

Materials used

The chemicals such as salicylaldehyde, thiourea, glycine of E. Merck grade and distilled ethanol were used. The melting points were determined using melting point apparatus and IR spectra were recorded in FT -IR Affinity-1 Shimadzu.

 

Drugs

Chlorpromazine (standard for CNS Depressant), Caffeine (standard for CNS stimulant) were chosen for our work.

 

Animals used

For the CNS depressant activity study sixteen albino rats of both sexes of weight 100-165g were used. The animals were kept in poly propylene cages in a dark/light cycle, 12hrs/12hrs and animals were fed with pelleted diet and drinking water ad libitum. All the experimental protocols were approved by the committee for the purpose of control and supervision on experiments on animals (CPCSEA), animal ethics committee vide number SBCP/ 2011-2012/ IAEC/ CPCSEA/6.

 

Methods used

a. Preparation of 1, 3-bis (2-hydroxybenzylidene) thiourea  Schiff base

Salicylaldehyde (0.02mol) and   thiourea (0.01mol) were taken in a RB flask   and refluxed with ethanol for 2hours. After refluxing, the product obtained was filtered, dried and recrystallized using ethanol.

 

Yield: 94%  m.p: 179.50C

 

b. Preparation of 2-(2-hydroxybenzylidene amino)acetic acid Schiff base

The Schiff base was synthesized by adding ethanolic solution of salicylaldehyde with alkaline solution of Glycine (0.01mole).  The mixture was refluxed for 2 hours. When a clear yellow solution was obtained.  The alkaline solution of Schiff base was acidified by ice cold dil. HCl and placed in ice bath for crystallization.

 

Yield:85%     m.p.:241⁰C

 

The structure of the compounds were proved by IR spectral studies as given inTable-1

 

Table-1.IR spectral data of the compounds

Compounds	.uC-N (cm-1)	uC=N (cm-1)	uC=O (cm-1)	uOH (cm-1)
BHBT	1100	1610	1680	3330
HBAA	-	1640	1700-1725	3250-3100

*BHBT- 1,3-bis(2-hydroxybenzylidene)thiourea

*HBAA- 2-(2-hydroxybenzylidene amino)acetic acid 

 

Determination of CNS activity ²⁰

Preparation of the drug for the experimental study

Schiff base and the standard drugs were administered in the form of suspension in water with 1% Sodium Carboxy Methyl Cellulose (SCMC) as suspending agent.

Locomotor activity

Locomotor activity was recorded with using Actophotometer (digital activity cage). The animals were divided into four groups (n = 4). Each rat was individually placed in the actophotometer for 10 min. Animals of group 1 were intraperitoneally treated with Caffeine (30 mg/kg) (i.p). Group 2 was treated orally with Chlorpromazine (30 mg/kg, i.p.). Group 3 was treated orally with 250 mg/kg of 1,3-bis(2-hydroxybenzylidene)thiourea drugs and group 4 was treated orally with 250 mg/kg of 2-(2-hydroxybenzylidene amino)acetic acid dose levels of drugs. Basal reaction time was noted before and 30 min after the administration of treatment. Account was recorded when the beam of light falling on the photocell of actophotometer was cut off by rat. Sample 1 received reference standard Chlorpramazine at a dose of 3 mg/kg (i.p.) 30 min before the test. Mean change in the locomotor activity was recorded for each group and were listed in Table -2.

 

RESULTS AND DISCUSSION:

The following result for CNS depressant activity was observed for the Schiff bases.

 

a. 1,3-bis(2-hydroxybenzylidene)thiourea

The dose dependent depression in the locomotor activity was found to be 60.54% for 3mg/kg of chlorpromazine and 41.17% for 250mg/kg of 1,3- bis (2-hydroxy benzylidene) thiourea.

 

Lower depressant activity was observed for the above Schiff base than that of chlorpromazine with a probability <0.5.

 

b. 2-(2- hydroxybenzylidene amino) acetic acid

The dose dependent depression in the locomotor activity was 60.54% for 3mg/kg of chlorpromazine and 69.71% for 250mg/kg of 2-(2- hydroxyl benzylidene amino) acetic acid. Higher depressant activity was observed for the above Schiff base than that of chlorpromazine with a probability <0.5.

 

 

Table -2. Locomotor activity of 1, 3-bis (2-hydroxybenzylidene)thiourea and 2-(2-hydroxybenzylidene amino)acetic acid.

Drug treatment	Dose (mg/kg)	Before treatment	After treatment	% change in activity
caffeine	30 mg/kg (i.p)	66.5±4.7346	108.75±3.4003	63.99
Chlorpromazine	3 mg/kg (p.o.)	85.25±9.1321	34±6.9880	60.54
BHBT	(250 mg/kg) p.o	76.75±1.8874	45.25±5.2181	41.17
HBAA	(250 mg/kg) p.o	98.25±12.5987	29.5±1.8484	69.71

 

One way ANOVA
F	2.695703	59.66224
df	(3, 12)	(3, 12)
P	(<0.5,<0.5)	<0.5

 

Parameter	chlorpromazine		BHBT		HBAA
	Before	After	Before	After	Before	After
t values	1.6194	11.0791	0.7341	1.6674	1.1228	0.6669
P-values	<0.5	<0.001	<0.5	<0.5	<0.5	-

Among these two 1,3- bis (2-hydroxy benzylidene) thiourea and 2-(2- hydroxyl benzylidene amino)acetic acid Schiff bases, 2-(2- hydroxyl benzylidene amino)acetic acid was found to possess highest depressant activity than that of chlorpromazine with a probability <0.5.

 

CONCLUSION:

The two Schiff bases 1,3- bis (2-hydroxy benzylidene) thiourea and 2-(2- hydroxyl benzylidene amino)acetic acid were derived from salicylaldehyde, thiourea and glycine by standard procedure.CNS activity of 1,3- bis (2-hydroxy benzylidene) thiourea (41.17%) and 2-(2- hydroxyl benzylidene amino)acetic acid (69.71%) Schiff bases, 2-(2- hydroxylbenzylidene amino)acetic acid possess highest CNS depressant activity than that of chlorpromazine (60.54%) with a probability <0.5.

 

REFERENCE:

1.       S.A. Sadeek, M.S. Refat, J. Korean Chem. Soc. 2006;50 (2): 107.

2.       S. Ren, R. Wang, K. Komatsu, P. Bonaz-Krause, Y. Zyrianov, C.E. Mckenna, C. Csipke, Z.A. Tokes, E.J. Lien, J. Med. Chem. 2006;45:  410.

3.       N. Chitrapriya, V. Mahalingam, L.C. Channels, M. Zeller, F.R. Fronczek, K. Natarajan, Inorg. Chim. Acta. 2008;361: 2841.

4.       M.S. Refat, S.A. El-Korashy, D.N. Kumar, A.S. Ahmed, Spectrochim.Acta Part A. 2007; 70: 898.

5.       R.Prabhakaran, R. Huang, K. Natarajan, Inorga. Chim. Acta. , 2006; 359: 3359.

6.       K.P. Balasubramanian, K. Parameswari, V. Chinnusamy, R. Prabhakaran, K. Natarajan, Spectrochim. Acta Part A 2006; 65: 678.

7.       R. Prabhakaran, A. Geetha, M. Thilagavathi, R. Karvembu, V.Krishnan, H. Bertagnolli, K. Natarajan, J. Inorg. Biochem. 2004; 98: 2131.

8.       S. Kannan, R. Ramesh, Polyhedron. 2006; 25: 3095.

9.       S. Kannan, K. Naresh Kumar, R. Ramesh, Polyhedron.2008; 27: 701.

10.     M. Sivagamasundari, R. Ramesh, Spectrochim. Acta Part A. 2007; 67: 256.

11.     S. Kannan, R. Ramesh, Y. Liu, J. Organomet. Chem. 2007; 692:3380.

12.     V Mahalingam, R. Karvembu, V. Chinnusamy, K. Natarajan,  Spectrochim. Acta Part A. 2006; 64: 886.

13.     G. Venkatachalam, R. Ramesh, Inorg. Chem. Commun. 2006; 9:703,.

14.     R. Ramesh, Inorg. Chem. Commun. 2004; 7: 274.

15.     R. Karvembu, S. Hemalatha, R. Prabhakaran, K. Natarajan, Inorga. Chem. . 2003; 6: 486.

16.     M. Jesmine, M.M Ali, M.S. Salahuddin, ABDLSEED and S. BEN- G. Weirif E-Journal of chemistry.2007; 4:461-466.

17.     C. Z. Kafka, J. Punocharova, Chem. Listy. 2000; 94:909.

18.     A. Valent, M. Melnik, D. Hudecova, B. DUDOVA, R. Kivekas, M. R. Sunberg, Inorg. Chim. Acta.2002; 15: 340.

19.     P.K.Sasmal, A.K. Patra, M. Nethaji, A.R.Chakravarty, Inotg. Chem.2007; 46: 1112.

20.     G.Valli, A.Vasanthi, R.Vijayalakshmi A.Thanga Thirupathi, Research. J. Pharm. Tech. 2011; 4(9)

 

 

 

Received on 19.10.2012        Modified on 22.10.2012

Accepted on 25.10.2012        © AJRC All right reserved