Claims:I/We claim:
1. A novel compound(s) of formula I or salt thereof comprising:
Wherein
R is selected from hydrogen, C1 to C4 alkyl, C1 to C4 alkoxy, nitro and halogen; and
m is an integer ranging from 1 to 4.
2. The compound(s) of formula I as claimed in claim 1, wherein C1 to C4 alkyl is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl; preferably methyl.
3. The compound(s) of formula I as claimed in claim 1, wherein C1 to C4 alkoxy is selected from methoxy, ethoxy, propyloxy, isopropyloxy, n-butyloxy, sec-butyloxy, iso-butyloxy, tert-butyloxy; preferably methoxy.
4. The compound(s) of formula I as claimed in claim 1, wherein halogen is selected from fluorine, chlorine, bromine, iodine; preferably fluorine, chlorine, bromine.
5. The compound(s) of formula I as claimed in claim 1, wherein m is 1 to 2.
6. The compound(s) of formula I as claimed in claim 1, wherein the compound(s) is selected from (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)propanoyl chloride, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-bromobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-bromobenzo[d]thiazol-2-yl)acetamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-methylbenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-methylbenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-nitrobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-nitrobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(benzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(benzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-methoxybenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-methoxybenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-nitrobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-chlorobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-chlorobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-fluorobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-fluorobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-chlorobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-chlorobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-methoxybenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-methoxybenzo[d]thiazol-2-yl)propanamide,
7. A process for synthesis of compound(s) of formula I as claimed in any claim of 1 to 6, wherein the process comprises the steps of:
a) refluxing a compound of formula A and hydrazine sulphate in a solvent for a time period in the range of 5 to 8 hrs to obtain a compound of formula B;
b) dissolving the compound of formula B in a solvent and adding a compound of formula B (i) and refluxing for time period in the range of 16 to 18 hrs under continuous stirring to obtain a compound of formula C;
c) refluxing a solution comprising the compound of formula C, a compound of formula D, and a base in a solvent for a time period in the range of 22 to 26 hrs to obtain the compound of formula I;

8. A pharmaceutical composition comprising
i. the compound(s) of formula I as claimed in claim 1; and
ii. a pharmaceutically accepted carrier.
, Description:
FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patent Rules 2003
COMPLETE SPECIFICATION
(see sections 10 & rule 13)
1. TITLE OF THE INVENTION
“NOVEL ANTI-CONVULSANT COMPOUNDS AND PROCESS FOR SYNTHESIS THEREOF”

2. APPLICANT (S)
NAME NATIONALITY ADDRESS
Dr. Bhusnure O.G.
Dr. Giram P. S.
Mr. Lonikar N.B. Indian Channabasweshwar Pharmacy College (Degree), Kava Road, Latur-413512, Maharashtra, India
3. PREAMBLE TO THE DESCRIPTION
COMPLETE SPECIFICATION
The following specification particularly describes the invention and the manner in which it is to be performed

FIELD OF INVENTION
The present invention relates to novel compounds, most particularly, indole containing marine alkaloids. Furthermore, it relates to a process for synthesis of said compounds. The said synthesised indole containing marine alkaloids have biological activity, especially anti-convulsant activity.
BACKGROUND OF INVENTION
Anti-convulsants (more commonly known as anti-epileptic drugs or recently as anti-seizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anti-convulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anti-convulsants suppress the excessive rapid firing of neurons during seizures. Anti-convulsants also prevent the spread of the seizure within the brain (https://en.wikipedia.org/wiki/Anticonvulsant).
Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, anti-neoplastic, anti-convulsant, anti-bacterial and anti-microbial activities, in addition to the action on human enzymes and receptors (Netz et al. “Marine Indole Alkaloids” Mar. Drugs 2015, 13(8), 4814-4914).
It is seemed that human adenosine receptor A2a antagonist acts as excellent supplementary therapy along with Dopamergic therapy in treatment of the Parkinson’s disease. The indole containing marine alkaloids are well known for their biological potential and CNS permeation. Some of the marine alkaloids are explored for other CNS potentials but their probable biochemical mode of action is still unknown. The study revealed these marine alkaloids are having excellent binding affinity towards human adenosine receptor A2a. Their binding revealed some interesting facts that these alkaloids are not only binding with the active side but also occupying the nearby site also which can contributes towards the antagonistic potential of these alkaloids. Insilco docking and pharmacokinetic analysis of the topsentin C and 6'-debromohamacanthin advocates the utility of the indole ring in the development of potent Human adenosine receptor A2a antagonist. Molecules developed via bridging two indole nucleus via pyridine nucleus will be an utilizable chemical scaffolds for Human adenosine receptor A2a antagonism.
The maximal electroshock induced convulsion in animals represents grandmal type of epilepsy. The tonic extensor phase is selectively abolished by the drugs effective in generalized tonic clonic seizure. The most outstanding action of phenytoin showed abolition of tonic extensor phase of MES seizure many drugs that increase the brain content of Gama amino butyric acid (GABA) have exhibited anticonvulsant activity against seizures induced by MES. There are numerous molecular mechanisms through which drugs can block seizure spread and or elevate seizure threshold.
In most cases, the synthesis of indole alkaloids were inspired by the naturally occurring molecules and their similarity to serotonin.
The indole alkaloids from plant sources are quite complex compared to synthetic. The importance of synthetic indole alkaloids is already established as the structure is available in various ligand receptors, enzyme inhibitors and modulators bio-receptor. Some of the naturally occurring indole alkaloids cannot be synthesized by currently know methods. In addition, most of the information on the effectiveness of indole alkaloids was reported from synthetic indole alkaloids. As a result the potential of many naturally occurring indole alkaloids as new drug leads for various psychiatric disorders is still untapped.
Several indole alkaloids have been employed as anti-depressants or provide lead structures for its development. Indole alkaloids which are valuable starting points for the development of future anti-depressants.

OBJECTS OF THE INVENTION
Main object of the present invention is to provide novel indole containing marine alkaloids compounds.
Another object of the present invention is to provide a process for synthesis of said indole containing marine alkaloids compounds
Another object of the present invention is to provide screening of synthesised indole containing marine alkaloids compounds for biological activities.
SUMMARY OF THE INVENTION
One of the aspects of the present invention is to provide a novel anti-convulsant compound(s) of formula I or salt thereof comprising:
Wherein
R is selected from hydrogen, C1 to C4 alkyl, C1 to C4 alkoxy, nitro and halogen; and
m is an integer ranging from 1 to 4.
Another aspect of the present invention is to provide a process for synthesis of anti-convulsant compound(s), wherein the process comprises the steps of:
a) refluxing a compound of formula A and hydrazine sulphate in a solvent for a time period in the range of 5 to 8 hrs to obtain a compound of formula B;
b) dissolving the compound of formula B in a solvent and adding a compound of formula B (i) and refluxing for time period in the range of 16 to 18 hrs under continuous stirring to obtain a compound of formula C;
c) refluxing a solution comprising the compound of formula C, a compound of formula D, and a base in a solvent for a time period in the range of 22 to 26 hrs to obtain the compound of formula I;

BRIEF DESCRIPTION OF THE FIGURES
Figure 1 illustrates anti-convulsant activity of synthesized compounds by MES induced model.
Figure 2 shows effect of synthesized compounds on lipid peroxidation level in rat brain tissue in MES induced model.
Figure 3 shows effect of synthesized compounds on Catalase level in rat brain tissue.
Figure 4 depicts effect of synthesized compounds on glutathione (GSH) level in rat brain tissue.
Figure 5 shows effect of synthesized compounds on SOD level in rat brain tissue.
DETAILED DESCRIPTION OF THE INVENTION
One of the embodiments of the present invention provides a novel anti-convulsant compound(s) of formula I or salt thereof comprising:
Wherein
R is selected from hydrogen, C1 to C4 alkyl, C1 to C4 alkoxy, nitro and halogen; and
m is an integer ranging from 1 to 4; preferably m is ranging from 1 to 2.
Another embodiment of the present invention provides a novel anti-convulsant compound(s) of formula I or salt thereof, wherein C1 to C4 alkyl is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl; preferably methyl.
Another embodiment of the present invention provides a novel The anti-convulsant compound(s) of formula I or salt thereof, wherein C1 to C4 alkoxy is selected from methoxy, ethoxy, propyloxy, isopropyloxy, n-butyloxy, sec-butyloxy, iso-butyloxy, tert-butyloxy; preferably methoxy.
Another embodiment of the present invention provides a novel anti-convulsant compound(s) of formula I or salt thereof, wherein halogen is selected from fluorine, chlorine, bromine, iodine; preferably fluorine, chlorine, bromine.
Another embodiment of the present invention provides a novel anti-convulsant compound(s) of formula I or salt thereof, wherein m is 1 to 2.
In another embodiment of the present invention there is provided a novel anti-convulsant compound(s) of formula I or salt thereof, wherein the intermediate compounds used for synthesis of compound of formula I or salt thereof are provided below:

Another embodiment of the present invention provides a compound of formula B (i), wherein X is halogen selected from a group consisting of fluorine, chlorine, bromine, iodine; preferably chlorine.
Another embodiment of the present invention provides a compound of formula B (i), wherein m is an integer ranging from 1 to 4; preferably m is 1 to 2.
Another embodiment of the present invention provides a compound of formula C, wherein m is an integer ranging from 1 to 4; preferably 1 to 2 and X is halogen selected from fluorine, chlorine, bromine, iodine; preferably chlorine.
Another embodiment of the present invention provides a compound of formula D, wherein R is selected from hydrogen, C1 to C4 alkyl, C1 to C4 alkoxy, nitro and halogen.
Yet another embodiment of the present invention provides a compound of formula D, wherein C1 to C4 alkyl is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl; preferably methyl, and wherein C1 to C4 alkoxy is selected from methoxy, ethoxy, propyloxy, isopropyloxy, n-butyloxy, sec-butyloxy, iso-butyloxy, tert-butyloxy; preferably methoxy.
Another embodiment of the present invention provides a novel anti-convulsant compound(s) of formula I or salt thereof, wherein the compound(s) is selected from (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)propanoyl chloride, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-bromobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-bromobenzo[d]thiazol-2-yl)acetamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-methylbenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-methylbenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-nitrobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-nitrobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(benzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(benzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-methoxybenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-methoxybenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-nitrobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-chlorobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-chlorobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-fluorobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-fluorobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-chlorobenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(7-chlorobenzo[d]thiazol-2-yl)propanamide, (Z)-2-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-methoxybenzo[d]thiazol-2-yl)acetamide, (Z)-3-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(6-methoxybenzo[d]thiazol-2-yl)propanamide.
In another embodiment of the present invention there is provided a novel anti-convulsant compound(s) of formula I or salt thereof, wherein the compound of formula I is selected from the compounds provided below.










In another embodiment of the present invention there is provided a process for synthesis of compound(s) of formula I or salt thereof, wherein the process comprises the steps of:
a) refluxing a compound of formula A and hydrazine sulphate in a solvent for a time period in the range of 5 to 8 hrs to obtain a compound of formula B;
b) dissolving the compound of formula B in a solvent and adding a compound of formula B (i) and refluxing for time period in the range of 16 to 18 hrs under continuous stirring to obtain a compound of formula C;

c) refluxing a solution comprising the compound of formula C, compound of formula D, and base in a solvent for a time period in the range of 22 to 26 hrs to obtain the compound of formula I;
Another embodiment of the present invention provides a method for synthesis of Schiff base of formula (A), wherein the solvent is selected from polar or nonpolar solvent. The solvent including such as but not limit to alcohols, ethers, ketones, acids, esters, acetonitrile (ACN) halogenated solvent(s); For example pyridine, xylene, toluene, n-hexane, cyclohexane, n-heptane, diethylether, diisopropylether, ter-butylmethylether, acetonitrile (ACN), tetrahydrofuran, dioxane, methylethylketone, acetone, dimethylformamide, chloroform, methanol, ethanol, propanol, butanol, pentanol, tert-butanol, 2-methyl-2-butanol, acetonitrile, methylene chloride and combinations thereof.
In an embodiment of the present invention, the base that can be used in the said processes includes but is not limited to organic bases such as ammonia, diethyl amine, triethylamine, di-isopropylethylamine (DIPEA), pyridine, dimethylaminopyridine (DMAP), imidazole; and inorganic bases including such as but not limited potassium carbonate, sodium carbonate, lithium carbonate, sodium bicarbonate, sodium hydroxide, lithium hydroxide, calcium hydroxide, potassium hydroxide, sodium alkoxide (for example sodium ethoxide, sodium-methoxide), magnesium hydroxide, and combinations thereof.
In another embodiment of the present invention there is provided a pharmaceutical composition, wherein the composition comprises:
i. anti-convulsant compound(s); and a pharmaceutically accepted carrier.
The invention is further illustrated by working examples as detailed below. The examples are meant for illustrative purposes only and are not meant imply restriction to the scope of the disclosure in any manner.
EXAMPLES
1) Synthesis of 3-(hydrazonomethyl)-1H-indole (compound of formula B)
Equimolar concentration of Indole-3-carboxaldehyde (0.01M) (compound of formula A) and hydrazine sulphate (0.01M) were refluxed in 25 ml ethanol for 6 hours in water bath, after completion of reaction the mixture was poured in crushed ice and recrystallize by using ethanol. Melting point: 1640C.
2) Synthesis of 3-(2-((1H-indol-3-yl)methylene) hydrazinyl) propranoyl chloride (compound of formula C)
0.01M gm of 3-(Hydrazonomethyl)-1H-indole (compound of formula A) compound was dissolved in 20 ml acetone by stirring the mixture on magnetic stirrer for 10 minute. After these added 0.01M chloropropionyl chloride and 0.01M triethylamine with continuous stirring. The mixture was reflexed for 17 hours with occasional stirring. The mixture was poured in crushed ice. The product was filtered and recrystallized the product in acetone. Melting point: 117oC.
3) Synthesis of 3-2-(1H-indol-3-yl)methylene)hydrazinyl)-N-(benzo[d]thiazol-2yl) Propranamide (compound of formula I):
0.01M of 3-(2-((1H-indol-3-yl) methylene) hydrazinyl) propranoyl chloride compound was dissolved in 10 ml tetrahydrofuran with stirring in magnetic stirrer for 10 minute. Then added solution of 0.01M 2-aminobenzothiazole in 5 ml tetrahydrofuran. After 05 minutes added a solution of 0.001M triethylamine dissolved in 5ml tetrahydrofuran with constant stirring. Later 0.005M potassium carbonate was added and refluxed the mixture for 24 hrs. After completion of reaction the mixture was poured in crushed ice. The product was filtered and recrystallized in ethanol. Melting point: 213oC.

4) Synthesis of 3-(2-((1H-indol-3-yl)methylene) hydrazinyl) acetyl chloride (compound of formula E)
0.01M of 3-(Hydrazonomethyl)-1H-indole (1) compound was dissolved in 20 ml acetone by stirring the mixture on magnetic stirrer for 10 minute. After these 0.01M chloroacetyl chloride and 0.01M triethylamine was added with continuous stirring. The mixture was reflexed for 14 hours with occasional stirring. The mixture was poured in crushed ice. Product was filtered and recrystallized in acetone. Melting point: 89oC.
5) Synthesis of 3-2-(1H-indol-3-yl)methylene)hydrazinyl)-N-(benzo[d]thiazol-2yl) acetamide (compound of formula I)
0.01 M of 3-(2-((1H-indol-3-yl) methylene) hydrazinyl) acetyl chloride (compound of formula E) compound was dissolved in 10 ml tetrahydrofuran with stirring in magnetic stirrer for 10 minute. Then solution of 0.01M 2-aminobenzothiazole in 5 ml tetrahydrofuran was added in above solution. After 05 minutes, added a solution of 0.001M triethylamine dissolved in 5 ml tetrahydrofuran with constant stirring. Later, 0.005M potassium carbonate was added and refluxed the mixture for 24 hrs. After completion of reaction, the mixture was poured in crushed ice. The product was filtered and recrystallized in ethanol. Melting point: 122oC.
6) Characterization of synthesised compounds of formula I
a) NL-1 (compound of formula E)
IR (KBr, cm-1): 3369.17 (NH stretching), 1124.01 (C-N stretching), 1631.17 (C=O Stretching), 1576.67 (C=N stretching), 740.76 (Ar- Cl)
1H NMR: ([D] DMSO): d 1.18 (s, 2H -CH2), 3.06 (s, 1H,-CH), 9.93(s, 1H, NH), 7.23-7.50 (d, 2H, Ar-H), 8.08-8.29(d, 2H, Ar-H),
13C NMR ([D] DMSO): d = 45.27 (-CH2), 112-123 (Ar-C), 134-136(=CH) 184.89 (C=O)
EIMS (M/z): Molecular weight Correspond to 235.5 molecular ion peak.
b) NL-2 (compound of formula C)
IR (KBr, cm-1): 3166.09 (NH stretching), 1149.10 (C-N stretching), 1629.29 (C=O Stretching), 1575.71 (C=N stretching), 755.33 (Ar-Cl)
1H NMR: ([D,] DMSO): d 1.16-1.21 (s, 2H -CH2), 3.06 (s, 1H,-CH), 7.29-7.52 (d, 2H, Ar-H), 8.07-8.29(d, 2H, Ar-H), 9.93(s, 1H, NH Indole), 12.18(s, 1H, NH)
13C NMR ([D,] DMSO): d = 45.40 (-CH2), 112-124 (Ar-C), 137-138(=CH) 184.89 (C=O)
EIMS (M/z): Molecular weight Correspond to 252.1 molecular ion peak
c) NL-3 (compound II)
IR (KBr, cm-1): 3268.17 (NH stretching), 1110.26 (C-N stretching), 1631.91 (C=O Stretching), 1577.86 (C=N stretching), 738.70 (Ar- Br)
1H NMR: ([D,] DMSO): d 1.16 (s, 2H -CH2), 7.19-8.29 (m, 9H, Ar-H), 9.93(s, 1H, NH Indole), 12.17(s, 1H, NH)
13C NMR ([D] DMSO): d = 54.01 (-CH2), 110-124 (Ar-C), 130-138(=CH) 178.10 (C=O)
EIMS (M/z): Molecular weight correspond to 438.2 molecular ion peak
d) NL-4 (compound XII)
IR (KBr, cm-1): 3167.47 (NH stretching), 1120.34 (C-N stretching), 1633.07 (C=O Stretching), 1574.20 (C=N stretching), 741.73 (Ar- Br)
1H NMR: ([D] DMSO): d 1.17-1.27 (2s, 2H -CH2), 1.31-1.35 (s, 2H -CH2), 7.19-8.46 (m, 9H, Ar-H), 9.93(s, 1H, NH Indole), 12.19(s, 1H, NH)
13C NMR ([D] DMSO): d = 32.80 (-CH2), 46.20 (-CH2), 112-131 (Ar-C), 137-138(=CH) 184.92 (C=O)
EIMS (M/z): Molecular weight Correspond to 442.4 molecular ion peak
e) NL-5 (compound VI)
IR (KBr, cm-1): 3378.44 (NH stretching), 1108.58 (C-N stretching), 1631.73 (C=O Stretching), 1599.20 (C=N stretching)
1H NMR: ([D] DMSO): d 1.17-1.27 (2s, 2H -CH2), 1.31-1.35 (s, 2H -CH2), 7.19-8.29 (m, 9H, Ar-H), 9.93(s, 1H, NH Indole), 12.17(s, 1H, NH)
EIMS (M/z): Molecular weight Correspond to 361.1molecular ion peak
f) NL-6 (compound XVI)
IR (KBr, cm-1): 2917.47 (NH stretching), 1123.05 (C-N stretching), 1631.04 (C=O Stretching), 1576.46 (C=N stretching)
1H NMR: ([D] DMSO): d 1.16-1.21 (2s, 2H -CH2), 3.02(s, H –CH3), 7.19-8.29 (m, 9H, Ar-H), 9.93(s, 1H, NH Indole), 12.18(s, 1H, NH)
EIMS (M/z): Molecular weight Correspond to 376.2 molecular ion peak
g) NL-7 (compound IX)
IR (KBr, cm-1): 3430.85 (NH stretching), 1123.42 (C-N stretching), 1623.66 (C=O Stretching), 1519.49 (C=N stretching); 1H NMR: ([D,] DMSO): d 1.23-1.35 (s, 2H -CH2), 7.21-8.82 (m, 9H, Ar-H), 9.93(s, 1H, NH Indole), 12.15(s, 1H, NH); EIMS (M/z): Mol. wt. correspond to 394.0 molecular ion peak
h) NL-8: (compound XIX):
IR (KBr, cm-1): 3367.89 (NH stretching), 1120.56 (C-N stretching), 1633.84 (C=O Stretching), 1573.51 (C=N stretching); 1H NMR: ([D,] DMSO): d 1.17-1.35 (2s, 2H -CH2), 7.19-8.46 (m, 9H, Ar-H), 9.93(s, 1H, NH Indole), 12.19(s, 1H, NH); EIMS (M/z): Molecular weight Correspond to 410.3 molecular ion peak.
7) Anti-convulsant activity of synthesized compounds
Anti-convulsant activity of synthesized compounds are performed as per reported method which are shown in below table 1.
Table 1: Anticonvulsant activity of synthesized compounds
Treatment
(dose, mg/kg, i.p) Maximal electroshock seizure test
Mean duration of tonic hindleg extension (THLE)
± SEM (s) No. of animals recovered Protection against mortality (%)
Control 09.49 ± 1.07 3/6 50.00
Phenytoin (20) Absence of extension 6/6 100.00
NL3 12.83 ± 0.61 4/6 66.66
NL5 08.59 ± 0.42 3/6 50.00
NL7 11.73 ± 0.71 2/6 33.33
NL4 10.05 ± 0.79 1/6 16.66
NL6 Absence of extension 6/6 100.00
NL8 02.18 ± 0.86 6/6 100.00
NL 2(2) 08.14 ± 0.43 3/6 50.00
NL 2(3) 02.21 ± 0.81 6/6 100.00
NL 2(4) 13.00 ± 0.79 1/6 16.66
NL 2(6) 09.71 ± 0.54 3/6 50.00
NL 2(7) Absence of extension 6/6 100.00
NL 2(8) 12.39 ± 0.42 2/6 33.33
Values are expressed in mean ± SEM, where n = 6. *P<0.05, P < 0.001;P<0.01, compared with vehicle treated group

Antioxidant Enzymes of the brain homogenate of the anticonvulsant activity of synthetic compounds by MES induced model
Effect of synthesized compounds on Lipid peroxidation level in rat brain tissue in MES induced model is showed in table 2.
Table 2: Effect of synthesized compounds on Lipid peroxidation level in rat brain tissue in MES induced model.
Experimental group OD Lipid peroxidation
n moles of MDA/mg of protein Decrease in MDA
(%)
Control 1.557 0.998
Phenytoin (20) 0.764 0.489 ± 0.012** 51.10
NL3 1.058 0.678 ± 0.012** 32.20
NL5 1.157 0.741 ± 0.003** 25.90
NL7 1.316 0.843 ± 0.010* 15.70
NL4 1.456 0.933 ± 0.007* 06.70
NL6 0.906 0.580 ± 0.009*** 42.00
NL8 0.858 0.550 ± 0.007*** 45.00
NL 2(2) 1.016 0.651 ± 0.004** 35.10
NL 2(3) 0.758 0.485 ± 0.001*** 51.50
NL 2(4) 1.164 0.746 ± 0.002* 25.40
NL 2(6) 1.064 0.682 ± 0.003** 31.80
NL 2(7) 0.864 0.553 ± 0.008*** 44.70
NL 2(8) 1.214 0.778 ± 0.003* 22.20
Effect of synthesized compounds on glutathione (GSH) level in rat brain tissue is showed in table 3.
Table 3: Effect of synthesized compounds on glutathione (GSH) level in rat brain tissue.
Experimental group OD Glutathione
µmoles/mg of protein
Normal 0.020 55.39 ± 1.68
Control 0.040 49.67 ± 2.08
Phenytoin (20) 0.025 53.96 ± 1.91***
NL3 0.050 46.81 ± 1.66**
NL5 0.026 53.67 ± 1.67**
NL7 0.030 52.53 ± 1.71*
NL4 0.050 46.81 ± 2.19*
NL6 0.030 52.53 ± 1.92***
NL8 0.022 54.81 ± 1.21***
NL 2(2) 0.031 52.24 ± 1.18**
NL 2(3) 0.023 54.53 ± 1.21***
NL 2(4) 0.046 47.95 ± 1.64*
NL 2(6) 0.080 38.22 ± 2.91**
NL 2(7) 0.027 53.38 ± 1.20***
NL 2(8) 0.090 35.36 ± 2.89*
Effect of synthesized compounds on Catalase level in rat brain tissue is showed in table 4.
Table 4: Effect of synthesized compounds on Catalase level in rat brain tissue.
Samples Reading Catalase (U/ml)
Normal control 0.78 2.10 ± 0.07
Control (induced group) 0.87 1.81 ± 0.04
Phenytoin (20) 0.81 2.01 ± 0.06**
NL3 0.76 2.17 ± 0.02**
NL5 0.77 2.13 ± 0.03**
NL7 0.81 2.01 ± 0.04***
NL4 0.88 1.78 ± 0.04*
NL6 0.81 2.01 ± 0.04***
NL8 0.80 2.04 ± 0.02***
NL 2(2) 0.87 1.81 ± 0.02**
NL 2(3) 0.89 1.75 ± 0.04***
NL 2(4) 0.92 1.65 ± 0.04***
NL 2(6) 0.81 2.01 ± 0.04**
NL 2(7) 0.88 1.78 ± 0.04***
NL 2(8) 0.91 1.69 ± 0.04*
All values expressed as mean±SEM; n=6 mice in each group, by one-way ANOVA followed by Dunneet’s Multiple Comparison Test (compared with control group) *p<0.05, **p<0.01, and ***p<0.001
Effect of synthesized compounds on SOD level in rat brain tissue is showed in table 5.
Table 5. Effect of synthesized compounds on SOD level in rat brain tissue.
Samples Reading SOD (U/ml)
Normal 0.210 2.16 ± 0.09
Control 0.340 1.26 ± 0.01
Phenytoin (20) 0.230 2.02 ± 0.04**
NL3 0.210 2.16 ± 0.02**
NL5 0.370 1.06 ± 0.01**
NL7 0.330 1.33 ± 0.01*
NL4 0.310 1.47 ± 0.02*
NL6 0.250 1.88 ± 0.02***
NL8 0.260 1.81 ± 0.02***
NL 2(2) 0.390 0.92 ± 0.01**
NL 2(3) 0.240 1.95 ± 0.02***
NL 2(4) 0.380 0.99 ± 0.03*
NL 2(6) 0.240 1.95 ± 0.01**
NL 2(7) 0.220 2.09 ± 0.02***
NL 2(8) 0.350 1.20 ± 0.03*