Evaluation of Anticonvulsant Activity of Novel Substituted 2-Mercaptobenzimidazole Derivatives
Ravi N Tiwari1*, KG Bothara1, Gurmeet Singh Chhabra1 and Sarang Kulkarni2
1Department of Pharmaceutical Chemistry, NMIMS University Shirpur Campus Dist. Dhule (M.S) India
2Siddhant College of Pharmacy Sudumbare, Pune (M.S.) India
*Corresponding Author E-mail: ravisun4@rediffmail.com
ABSTRACT:
Mannich bases of sulphonamide substituted 2-mercaptobenzimidazole compounds were synthesized from 2-mercaptobenzimidazole by reacting with aldehyde like formaldehyde and the various sulphonamides. Synthesized compounds were characterized by spectral studies and evaluated for antibacterial activities. The statistical analysis was done by students“ t ”test and the values were expressed as Mean ± SEM.
KEYWORDS: Mannich Bases Sulphonamide Substituted 2-Mercaptobenzimidazole, Anti-Convulsant Activity.
INTRODUCTION:
A reaction between a compound having a reactive hydrogen atom, an aldehyde and a secondary amine1 became a general reaction by the name of Mannich. This reaction is useful in making N-methyl derivatives and many drug molecules. The drugs with 2-mercaptobenzimidazole moiety were found to possess anti-convulsant2, anti-estrogenic3, anti-microbial4, anti HIV5 and anti-tumour6 activities. All these observations and essential role of the substituted 2-mercaptobenzimidazole derivatives prompted us to synthesize various S-substituted 2-mercaptobenzimidazole and to evaluate their anti-convulsant activities.
MATERIAL AND METHODS:
Melting points were determined by open-ended capillary tube in the electrical melting point apparatus and are uncorrected and the purity of the compounds were checked by TLC using Silica Gel as stationary phase and the spots were visually detected in an Iodine chamber. The structure of the synthesized compounds was elucidated by FT-IR7 (Shizamadu-8400 series) in KBr disc and FT-1H NMR7 (Brucker 400 MHz) in DMSO-d6.
o-phenylenediamine [2.18gm] was dissolved in the solution of [1.44gm] of KOH in 20ml of methanol of 4ml of water. To this solution (CS2) carbon disulphide [1.28gm] was added slowly with constant shaking. The mixture was refluxed for 8 hrs.
The resultant solution was neutralized with ice cold acetic acid. Whole 2-mercaptobenzimidazole separated as colorless solid. It was filtered washed with cold water and recrystallize from CHCl3 petroleum ether mixture.
Equimolar quantities (0.01mole) of 2-mercaptobenzimidazole and secondary amine were dissolved in methanol (30 ml) in a beaker under perfect ice cold condition and stirred constantly and then 0.01 moles of series of aldehyde (such as formaldehyde and acetaldehyde) was added slowly and heated to reflux for 3hrs. The content was kept over night in the freezer. Crystallized product obtained was recrystallized from alcohol. The %yield, Rf value, melting point and spectral data were reported in Table 1.
Anti-convulsant activity [MES Method]:
The anti-epileptic activity was carried out by Maximal electrical shock induced convulsion method8. Adult albino mice of either sex weighing of 20 – 30 g were used for the study. Mice were treated with newly synthesized 2-mercaptobenzimidazole (20mg/kg,ip) and Std drug, Phenytoin (20mg/kg,ip). After 30 min, the animals were subjected to electro shock through ear electrodes of 150 mA for 0.2 sec by electro convulsiometer and the presence and absence of extensor response was noted and duration of time was analyzed statistically by students “ t ” test and expressed in Mean ± SEM and tabulated in Table 2.
RESULTS
Table 1: Physical Data of Newly Synthesized Compounds
Compd code |
Melting point oC |
Rf value |
Log P |
IR spectra (cm-1) |
1H NMR spectra |
RNT-1 |
140-143 |
0.3268 |
4.286 |
3480,1306,1463,1751, 3010,729 |
7.26 – 8.06(m, Ar-H), 5.78(s,CH2), 5.29(S, NH) |
RNT-2 |
128-131 |
0.5412 |
6.657 |
3427,1605,1300,1461, 719,776 |
7.12 – 7.41(m, Ar-H), 5.15(s, NH), 2.58(s, CH2) |
RNT-3 |
160-164 |
0.3227 |
5.343 |
3456,1663,1450,1470, 1300,1590,1350,748 |
7.16 – 7.32(m, Ar-H), 2.32(s,CH2), 5.54(s,NH) |
RNT-4 |
110-113 |
0.5228 |
4.567 |
3356,1461,1310,1616, 1350,741 |
7.18 – 7.96(m, Ar-H), 2.52 (s,CH2), 5.28(s, NH) |
RNT-5 |
180-184 |
0.6455 |
5.412 |
3452,3018,1302,1339, 1457,774,1610 |
7.33-7.88(m, Ar-H) 2.28(s,CH2), 5.11(s,NH) |
RNT-6 |
126-130 |
0.4588 |
6.552 |
3360,3039,1465,1294, 1615,1345,774 |
7.62 – 8.04(m, Ar-H), 2.77(s,CH2), 5.21(s,NH) |
RNT-7 |
170-173 |
0.3276 |
3.629 |
3453,1226,3030,1310, 1613,1652,772 |
7.32 – 7.92(m, Ar-H), 2.22 (s,CH2),5.42(s,NH), |
RNT-8 |
186-189 |
0.6289 |
6.348 |
3440,3063,1457,1330, 1605,1357,778 |
7.4 – 8.6(m, Ar-H), 7.21(s,NH), 2.32(s, CH2) |
Table 2: Anti-Convulsant Evaluation of Newly Synthesized Compounds
S. No. |
Treatment |
Duration (in sec) (Mean ± SEM) |
Recovery/ Death |
||
Extensor |
Clonus |
Stupor |
|||
1 |
Control |
31.50 ± 0.9220 |
22.66 ± 1.7638 |
69.33 ± 3.2830 |
Recovery |
2 |
Phenytoin Standard |
16.667 ± 1.0541** |
9.50 ± 0.9574** |
24.66 ± 2.1551** |
Recovery |
3 |
RNT-1 |
19.44 ± 1.5433** |
12.24 ± 0.8349** |
22.41 ± 1.7651** |
Recovery |
4 |
RNT-2 |
38.46 ± 1.2318 |
21.14 ± 1.1556 |
38.00 ± 1.5411 |
Recovery |
5 |
RNT-3 |
21.23 ± 0.9841** |
15.30 ± 0.8834** |
24.32 ± 1.1266** |
Recovery |
6 |
RNT-4 |
22.17 ± 1.1211** |
13.35 ± 0.6288** |
28.65 ± 1.8013** |
Recovery |
7 |
RNT-5 |
20.44 ± 1.6782** |
12.66 ± 1.9890** |
26.34 ± 1.6931** |
Recovery |
8 |
RNT-6 |
26.46 ± 1.8256* |
18.67 ± 1.7643* |
32.78 ± 2.3461* |
Recovery |
9 |
RNT-7 |
36.00 ± 1.8739 |
23.49 ± 1.8729 |
36.77 ± 1.8972 |
Recovery |
10 |
RNT-8 |
24.52 ± 1.9821* |
20.48 ± 1.8211* |
34.29 ± 1.5931* |
Recovery |
** P < 0.001 vs. control indicates highly significant, * P < 0.01 vs. control indicates moderately significant.
Totally a series of eight novel 2-mercaptobenzimidazole derivatives were synthesized and elucidated by spectral data and evaluated for their anti-convulsant activities. Compound RNT-1, RNT-3, and RNT-4 and RNT-5 has shown highly significant anti-convulsant activity due to the substitution with Phthalimide, Acetanilide, Indole and Piprazine respectively. Compound RNT-6 and RNT-8 shows moderate anti-convulsant activity. Compounds RNT-2 and RNT-7 were devoid from anti-convulsant activity. The maximum anti-convulsant activities were observed in the animals administered with 20 mg/kg body weight of the synthesized compounds as well as in those animals which received phenytoin (20 mg/kg).
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Received on 22.10.2009 Modified on 21.12.2009
Accepted on 23.01.2010 © RJPT All right reserved
Research J. Pharm. and Tech. 3(2): April- June 2010; Page 466-467