INTRODUCTION:

The wide class of pharmaceutical compounds with varied biological actions that are the result of using a benzodiazepine as a starting point includes antibacterial, hypnotic, anticonvulsant, analgesic, anti-inflammatory, anticancer, and neuroleptic^1-7. Not only are benzodiazepines important biologically, they are also effective starting materials for the synthesis of fused ring compounds such as triazolopyridines, thiazolopyridine, imidazolopyridines, oxodiazolopyridines, oxazolopyridines, furanylpyridines, and pyrimidylpyridines.

Due to its anticancer, anti-tubercular, anticancer, anti-malarial, and anti-inflammatory properties, substituted chalcones are utilised in the synthesis of benzodiazepines^8-11. The biological spectrum of benzodiazepines has been enhanced by the preparation of new derivatives of benzodiazepine-based chalcones. a large number of new substances were assessed for their anti-inflammatory properties^12-27.

METHODS:

The melting points were found in open-bottomed, uncorrected capillary tubes. An infrared (IR) spectrum was obtained using a Tensor 27 spectrophotometer (with a thin film support on KBr pellets) on the Bruker Optik (Germany) equipment. All 1H NMR spectra were captured on a Bruker 400 MHz spectrophotometer using CDCl3 as the solvent and tetramethylsilane as an internal standard. Using a Jeol-D-300 mass spectrometer (70 eV), a Shimadzu, Japan, mass spectrometer, the mass spectra were recorded. To assess the homogeneity of the compounds, the compound was dissolved in methyl nol: glacial acetic acid: CHCl3 (4:3:1) and spotted on silica gel-G coated plate to perform the mobility experiment. The synthesised compounds were all found to have good elemental analysis, and all were entered in the record.

General procedure:

Procedure for preparation of chalcones:

Sodium hydroxide solution was added to a round bottom flask containing 10ml of distilled water and 20ml of denatured ethanol, then 10ml of denatured ethanol was added to the round bottom flask containing the solution. A tub of crushed ice was used to submerge the flask. Freshly distilled acetophenone (molarity of 5.2g) was poured into the flask with the stirrer, and benzaldehyde (molarity of 4.4 mmol) was added to it. To achieve a 25-degree temperature and mixing, the mixture was swirled constantly. Stirred the reaction mixture into ice for the night, and then poured it into the preheated incubator. Water was first filtered and then washed with cold water until the washing neutral to litmus, after which the washing water was decanted and the product was recrystallized from spirits.

Synthesis of 2, 4 -disubstitued-1,5 benzodiazepines:

Two grammes of chalcone (0.01mol) were mixed with one gramme of o-phenylene diamine (0.01mol) and five millilitres of glacial acetic acid in DMF, and this mixture was placed in a conical flask and irradiated at 750 watts in the microwave for five minutes. The reaction mixture was allowed to reach room temperature, after which it was treated with methanol and returned to the refrigerator. Then, it was allowed to warm up and the cold ethanol crystallisation was performed.

Fig. 1: Scheme of synthesis of 2, 4 -disubstitued-1,5 benzodiazepines

Characterization:

The recrystallization step was used to purify the synthesised chemical. The chromatography analysis was completed by employing a thin layer chromatography plate. Iodine stain was used to detect the TLC plates after they were made using silica gel and the mobile phase was methanol: glacial acetic acid: CHCl3 (4:3:1). This melting point was determined using an open capillary tube method, and no corrections were made. shimadzu spectrophotometer was used to set a new IR record (Vels University). H NMR spectra were obtained using a Bruker 500 MHz spectrophotometer using tetramethylsilane as an internal reference. GCmate data was obtained using a JEOL mass spectrometer (Sophisticated analytical instrument facility, Indian institute of Technology, Chennai, Tamil Nadu, India). The computed mass of the compound was checked with the molecular mass on the graph to see if they matched.

Table 1: Structural information of derivatives

S. No.	Compound	R	R’
1	1a	Di hydroxy acetophenone	p-dimethyl amino benzaldehyde
2	1b	Di hydroxy acetophenone	3-ethoxy 4 hydroxy benzaldehyde
3	1c	Di hydroxy acetophenone	Salicylaldehyde
4	1d	p-chloro acetophenone	p-dimethyl amino benzaldehyde
5	1e	p-chloro acetophenone	anisaldehyde
6	1f	p-chloro acetophenone	cinnamaldehyde

Pharmacological Screening:

This entire project's animal experiment methods have been authorised by the Vel's College of Pharmacy's Institutional Animal Ethics Committee in Chennai, Tamil Nadu.

Acute Toxicity Studies in Mice:

Following OECD guidelines, a single-dose acute oral toxicity study was completed. 50-1000mg/ml in 2% CMC solution was used to create the benzodiazepine derivatives (a, 1b, 1c, 1d, 1e, 1f). For comparison, animals in the same group were fed 1000mg/kg body weight of each species (three animals per sex). Additionally, 2% CMC was provided to the control group, which consisted of two animals of each species. Mice and toxicity were examined continuously for 1 hour after the treatment, but signs of toxicity began to appear intermittently at 4 hours after administration and reappeared constantly for the next 24 hours. During the whole observation period, which was up to 14 days, the mice were monitored for any behavioural abnormalities or indications of toxicity or mortality, and the length of time until death.

Anti-inflammatory activity:

According to Winter et al, the anti-inflammatory properties of the test compounds were evaluated by using carrageenan-induced rat paw edoema and formalin-induced paw edoema techniques. Every experiment was carried out according to institutional animal ethics committee laws and regulations. Rats (150-200g) of either sex were injected with 0.1ml of 1 percent carrageenan in distilled water under the plantar surface of their left hind paws. Six creatures make up each group. During the maintenance, these animals were fed commercial food pellets and water ad libitum. During the experiment, they only ate food pellets and water. In conformity with acknowledged norms on animal testing, our experiments were undertaken. Intraperitoneal injection of the test compounds was done 30 minutes after the carrageenan injection. The 10mg/kg body weight dose of Diclofenac sodium was used as the benchmark. After 1, 2, 3, and 4 hours after carrageenan injection, the rat paw volume was assessed using a plethysmometer. The edoema volume was determined by calculating the difference between the paw volume at 4 hours and zero hours. Using the formula below, the percentage inhibition of paw edoema was calculated:

%Edema inhibition = 100(1−Vt/Vc), where Vt represents mean increase in paw volume of test and Vc represents mean increase in paw volume of control.

Anti oxidant activity:

A large body of evidence now supports the idea that antioxidants are molecules that can help defend your cells from free radical harm. Free radicals are formed when you consume or are exposed to tobacco smoke or radiation, and they cause degenerative disease. Free radicals may cause cell damage and are commonly associated with heart disease, cancer, and other disorders.

Method of assay:

(a) Hydrogen peroxide scavenging assay:

Chemicals: Hydrogen peroxide,phosphate buffer (pH 7.4), Gallic acid and extract.

Apparatus: Spectrophotometer and p^H meter.

Preparation of standard solution: Required quantity of Gallic acid was dissolved in to give (10, 20, 30, 40, 50) μg/ml

Preparation of Hydrogen peroxide solution: Required quantity of Hydrogen peroxide is dissolved in phosphate buffer to give 100mM solution with Ph 7.4

Preparation of sample solution: Required quantity of sample was dissolved in Phosphate buffer to give (100, 200, 400, 600, 800, 1000) μg/ml.

Procedure: Take 2mL of hydrogen peroxide solution and add 1mL of normal Gallic acid at different concentrations to it.

2mL of hydrogen peroxide solution is obtained, and 1 mL of various quantities of extract is added to it. Incubate the above-prepared solutions for 10 minutes.

Phosphate buffer was used as a blank and the absorbance was measured at 230nm.

Hydrogen peroxide scavenging activity:-

Despite not being extremely reactive, the hydroxyl radical generated by hydrogen peroxide can be damaging to cells. It is absolutely necessary to remove the hydrogen peroxide radical from the food system to ensure food safety. In the experiment, the capacity of extraction to scavenge was investigated. The results of the study, given in Table 4, reveal the free radical hydrogen peroxide against a standard using a bar chart. The graph depicts the samples' activity increasing in a concentration-dependent manner. strong radical scavenging activity when compared to the standard, Gallic acid (97.85 percent).

Table 2: Anti-inflammatory activity of substituted benzodiazepine derivatives (Carragen induced)

S. No.	Compound	Mean paw oedema value ± SD
S. No.	Compound	1 hr	2 hr	3 hr	4 hr
1	Control	0.98±0.03	0.82 ± .02	0.46± 0.02	0.33± 0.04
2	Standard	2.09 ±0.2*	1.93± 0.0363	1.87± 0.21**	1.7± 0.23
3	Compound 1a	0.361±0.004 **	0.361 ±0.004**	0.286± 0.003**	0.256± 0.004**
4	Compound 1b	0.39 ± 0.005**	0.355± 0.005**	0.30±0.003**	0.29 ± 0.004**
5	Compound 1c	0.45 ± 0.004**	0.42± 0.004 **	0.37±0.002**	0.23± 0.004**
6	Compound 1d	0.32 ± 0.007**	0.36± 0.005**	0.27±0.006 **	0.26± 0.007**
7	Compound 1e	0.26± 0.002**	0.271 ± 0.005 **	0.34±0.001*	0.39±0.004**

Table 3: Anti-inflammatory activity of substituted benzodiazepine derivatives (Formalin induced)

S. No.	Compound	Mean paw oedema value ± SD
S. No.	Compound	1 hr	2 hr	3 hr	4 hr
1	Control	0.96±0.04	0.82 ± .02	0.46± 0.02	0.32± 0.03
2	Standard	2.87 ±0.23**	2.35± 0.21**	2.04± 0.2**	1.95± 0.0363
3	Compound 1a	0.37±0.004 **	0.308 ±0.004	0.298± 0.003**	0.262± 0.004**
4	Compound 1b	0.38 ± 0.005**	0.351± 0.005**	0.33±0.003**	0.27 ± 0.004**
5	Compound 1c	0.47 ± 0.004**	0.42± 0.004 **	0.37±0.002**	0.23± 0.004**
6	Compound 1d	0.36± 0.005**	0.32± 0.007**	0.36±0.007 **	0.22± 0.006**
7	Compound 1e	0.39± 0.004**	0.34 ± 0.001 *	0.272±0.005*	0.26±0.002**

Table 4: Hydrogen peroxide scavenging activity of derivatives

S. No.	Conc µg/ml	% of inhibition
		Test drug Vit. E
		0 min	15 min	30 min	0 min	15 min	30 min
1	25	8.55±0.24**	12.62±0.866**	20.78±1.07	31.78±3.29	43.04±0.51	54.71±1.62
2	50	12.1±0.73	21.82±1.24**	30.18±1.62	39.57±0.54	50.12±1.2	59.21±0.72
3	100	33.97±3.66**	42.82± 0.43**	51.61±0.72	47.16±1.45	70.12±2.24	70.32±3.92
4	200	43.08±1.83**	51 .24±4.62**	59.24±2.72	53.72±2.08	64.81±0.59	76.21±1.47
5	400	52.76±3.03 *	60.12± 0.75**	69.12±2.16	62.21± 1.62	71.21±0.89	79.90± 1.24
6	800	59.94±1.06**	68.24±1.64 **	75.92±1.64	71.96±0.51	82 .77±2.62	93.16±4.92
7	1000	68.29±2.62*	82.22±2.24*	93.72±0.91	76.14± 0.84	86.77±2.62	97.24± 0.64
8	IC₅value	362 µg/ml	185 µg/ml	97.50µg/ml	145 µg/ml	50 µg/ml	18 µg/ml

(b) Nitric oxide scavenging activity:

Abnormally high quantities of free radicals and a corresponding decline in antioxidant defence mechanisms can lead to damage to cellular organelles and enzymes, as well as an increase in lipid peroxidation and the development of insulin resistance. oxidative stress adverse effects may lead to increased severity of illness. Nitric oxide (NO) is an unstable species under aerobic conditions. It connects with O2 to generate the stable compounds nitrates and nitrite, which it gets via connecting with O2 and a few other intermediates. This enzyme can affect several physiological processes, including the relaxation of smooth muscle, signalling in the nervous system, prevention of platelet aggregation, and the control of cell-mediated toxicity. Neuronal messenger, vasodilation, antibacterial, and anticancer capabilities are among the many applications of free radicals in biological systems. Nitric oxide is an exceedingly unstable species under aerobic conditions. It reacts with O2 to form the stable products nitrates and nitrite, which are created through intermediates such as NO2, N2O4, and N3O4. The Griess reagent is used to determine the correct solution. When present, the test chemical will reduce the quantity of nitrous acid. greater dosages showed valuable high radical scavenging activity in contrast to the benchmark for Ascorbic acid (93.85 percent ). Table 4 presents the results, along with a plot showing the same data, but with the standard present.

Chemicals required:

Sodium nitroprusside, phosphate buffersaline, sulfanlic acid, napthaline diamne dihydrochloride.

Preparation of reagents:

Sulfanilic acid reagent: 20% of glacial acetic acid was prepared by dissolving 20ml of glacial acetc acid in 100ml of distilled water, 0.33ml of sulfanilic acid is taken and is make up to 100ml wth 20% glacial acetic acid.

Napthyl Ethylene Diamine Diamine Dihydro Chloride (0.1%w/v): 0.1gm of napthyl ethylene damine dihydrochloride is dissolved n 100ml of distlled water.

Sodium nitroprusside (10mm): Molecular weight is 297.95gm n 1000ml = 1ml.

29.795gm in 1000ml = 0.1 ml, 2.9795gm in 1000ml= 0.01ml, 0.29795gm in 1000ml= 0.001ml, 0.2979 gm in 100ml =10mm.

To investigate the suppression of ntric oxide radicals, the hydrochloride salt of a molecule called N-napthyl ethylene diamine d- hydrochloride (0.1 percent weight/volume) was used. To determine if aqueous ethanolic extract has 500-1000mg/ml total aqueous extract and that the resulting reaction mixture comprises 2ml of 10mm sodium nitroprusside, 0.5 ml of saline phosphate buffer, and 0.5ml of standard solution (ascorbic acid or quercetin), incubate for 150 minutes at 25°C. A mixture of 0-5ml of the above incubation mixture and 33% n 20% glacial acetic acid was added to the previously incubated solution, and after 5 minutes the diazotzation process was complete.

Then, after it had stood for 30 minutes, 0.1mL of napthyl ethylene diamine hydrochloride was added, and the solution was agitated at 25degrees Celsius for another 30minutes. To measure the concentration of nitrile, 540nm was chosen and the nitrile solution was compared to a standard solution as a control.

Ascorbic acid and quercetin were used as standards, and the blank was used as a buffer and to build up solvents.

% Scavenging activity ={(Acontrol- Atest or Astd)}*100

Where, A control = Obsorbance of control

Table 5: Nitric oxide radical scavenging activity of benzodiazepine derivatives

S. No.	Concentration µg/ml	Inhibition
S. No.	Concentration µg/ml	Test drug	Vitamin C
1	25	36.08±0.68**	57.52±140
2	50	45.23±2.28**	64.53±0.46
3	100	53.01 ± 2.29**	73.07±2.54
4	200	67.03± 1.81**	78.02±0.85
5	400	75.25 ±0.85**	81.90± 0.22
6	800	84.05± 1.45**	87.96± 0.82
7	1000	88.58±0.95 **	96.04± 1.44
8	IC	37.5 µg/ml	13.5µg/ml

RESULTS AND DISCUSSION:

Additional information is provided with regard to the molecular formula and code number of the molecule, along with the melting point, yield, and Rf value. The spectroscopic diagnosis of the four typical substances yields the following results, the simple (2,6-dihydroxyphenyle) A/[B]6-dimethylamino-5H-benzo[b]caboxazole 2-hydroxyethanone (1a): A peak centred at cm-1 in the IR spectra of 1a is attributable to the stretching of the c=O bonds of the molecule.

In contrast to bands at 2981 cm-1 and 1592 cm-1, which are attired to stretching of C-H bonds of sp3 and sp2 carbons, the bands at 2912 cm-1 and 1661 cm-1 are attired to stretching of C-H bonds of sp2 and sp3 carbons.

Bending vibrations of C-C bonds are seen while studying the absorption band at 2318 cm-1.

The C-N stretching takes place at a wavelength of 1399 cm-1. This specific strong band in the range of 1032 cm-1 is a result of O-H bond bending. The intermediate wavelength bands of 3343 cm-1 and 753 cm-1 are indicative of the non-classical side-bending of an aromatic N-H stretching vibration out of plane. It may be inferred from the facts above that the structure of the molecule 1a is as follows.

(2,6-dihydroxyphenly)-4(3-ethoxy-4-hydroxy)phenyl)-5H-benzo 2-dimethylamino-1-propanol (1b). A prominent peak at 3343 cm-1 appears due to hydrogen-bonded N-H stretching in the IR spectra of the chemical 1b. In observing C-H (sp2) and C-H (sp3) stretching at 972 cm-1 and 750 cm-1, it is found that the H-H (sp2) and H-H (sp3) pairs exist as well. This aroma-bending frequency of 2982 cm-1 corresponds to the compound being a floral-musky aroma. a strong and distinct peak on the C=O functional group spectrum that appears about 1884 cm-1 indicates the presence of the C=O functional group In 1376 cm-1, the C-N stretching is detected. The 1122 cm-1 bands are representative of O-H stretching. On the basis of the aforesaid evidence, the structure of compound 1b is estimated to be structured as shown above. 4-hydroxyphenyl-2-2-dihydroxy-4-(4-hydroxyphenyl)benzo[b][1,4]diazepin-5-yl)methane (1c). The IR spectra of the compound 1c displays a dominant broad and shallow band with a centre wavelength of 3,844 cm-1. N-N bond is stretched. C-N bonds were detected at 3646 cm-1 and 3646 cm-1, while stretching occurred at 3095 cm-1. At 1780 cm-1, the band is identified as CONH. As is evident from the above, the structure of compound 1c can be represented as follows. N,N-dimethyl-2-chloro-N-benzylethylaniline (1d). A single wavelength in the infrared spectrum, with a wavelenth of 3291 cm-1, appears in the IR spectra of the chemical 1d. The lengthening of the N-Hbond has occurred as a result. C-H stretching at 2896 cm-1 and 1997 cm-1 belongs to the band at that frequency. Bands at 2056 cm-1 C-N bond respectively at 2056 cm-1 C-N. There is a considerable carbonyl stretching at 1648 cm-1. In the C-C band, the ratio of CH to CH2 is about 1432:1. C-Cl bonds are shown by the band at 1893. A series of interesting findings may be seen in the 1H NMR spectra of the chemical 1d. 4.6 sings the existence of nitrogen, 7.12 sings the presence of benzene, which is an aromatic benzene triplet, 6.5 reveals benzene of the diazepine molecule, and 2.85 sings the presence of dimethyl amine.

Further, this structure is supported by mass spectrum showing the M + peak at m/z 297.1, verifying the molecular mass of the suggested structure (calculated) is 297.1, in agreement with the computed molecular mass of the proposed structure. 4 dibenzo[b,f][1,4]diazepine (2-chloro-1-phenyl-1H-benzo[b][1,4]diazepine) (1e). N-H bond stretching results in a band at 3291 cm-1 in the IR spectra of the chemical 1d. C-H stretching at 2896 cm-1 and 1997 cm-1 belongs to the band at that frequency. The wavelength at 2056 cm-1, where C-N bonds form, is 2056 cm-1. At the 1648 cm-1 carbonyl stretching frequency, the carbonyl stretching displays a considerable level of effect. In the C-C band, the ratio of CH to CH2 is about 1432:1. The band at 1893 showcases the C-Cl bond at 7.13, which exhibits a benzene of diazepine with an armotric ring, while the triplet at 7.0 demonstrates the benzene of diazepine of diazepine armotric ring, and the quartet at 4.4 exhibits the presence of chlorine in the chemical.

This is supported by mass spectrometry At m/z 296.07, the M + peak is seen, and is consistent with experimental data as well as the structure of compound 1e. 2-chloro-1H-benzo[b][1,4]diazepin-2-one, 4-chloro-3-phenylacrolein (1f). Due to the stretching of the N-H bond, the IR spectra of 1d reveals a broad band at 3291 cm-1. C-H stretching is given to the band at 1997 cm-1 in the molecule. At 2056 cm-1, the C-N bonds each exist. At the 1648 cm-1 carbonyl stretching frequency, the carbonyl stretching displays a considerable level of effect. In the C-C band, the ratio of CH to CH2 is about 1432:1. C-Cl bonds are shown by the band at 1893. 7.58 hydrogen reveals the cinnamaldehyde single, 6.64 aromatic benzene shows the singlet, 7.25 aromatic benzene shows the single, and 6.5 benzene shows the benzene of diazepine Diazepine appears in the compound with the doublet at 4.0, and hydrogen appears in the molecule with the singlet at 4.6. Mass spectrum also confirms this structure. The M+ peak, which appears at m/z 308.7, shows that the predicted molecular mass of the structure is 308.7.

SUMMARY AND CONCLUSION:

Biological activity is derived from simple and complex chemical entities having molecular modifications. Compounds that have selective pharmacological action are derived through different techniques. Benzodiazepines and its related substances showed strong anti-inflammatory and anti-oxidant properties. This project was designed to identify novel synthesised compounds with potent anti-inflammatory and anti-oxidant properties. Following the above process, chalcones and ortho phenylene diamine were cyclized to give 2,4-disubstituted 1,5 benzodiazepine derivatives. A total of six syntheses have been completed, and the syntheses have been listed in the following table. Using IR 1H NMR and mass spectroscopy for diverse analyses. Using the findings of this study, it was determined that the benzodiazepine derivatives that were substituted expectedly were made. To see if these newly synthesised benzodiazepine compounds had anti-inflammatory and antioxidant properties, researchers tested them. 1b, 1d showed strong anti-oxidant action in the presence of a DPPH radical. It was revealed that scavenging activity of Compound 1c with a nitric oxide scavenging method had a positive effect on its anti-oxidant activity. Anti-inflammatory actions were discovered in all the five compounds (the ones labelled 1a, 1b, 1c, 1d, and 1e). In this investigation, benzodiazepine derivatives, synthesised by the described approach, had antioxidant and anti-inflammatory action that was particularly pronounced.

REFERENCES:

1. Ilango SS, Remya PU, Ponnuswamy S. Synthesis and antimicrobial activity of novel 1,5-benzodiazepines. Indian J Chem 2013;52B(01):136-40.

2. Kudo Y. Hypnotic effects of a benzodiazepine derivative: A clinical observation. Int Pharmacopsychiatry 1982;17(1):49-64.

3. De Sarro G, Gitto R, Rizzo M, Zappia M, De Sarro A. 1,4-Benzodiazepine derivatives as anticonvulsant agents in DBA/2 mice. Gen Pharmacol 1996;27(6):935-41.

4. Najafi N, Pirali M, Dowlatabadi R, Bagheri M, Rastkari N, Abdollahi M. Synthesis and analgesic and anti-inflammatory properties of new benzodiazepine derivatives. Pharm Chem J 2005;39(12):641-3.

5. Fruscella P, Sottocorno M, Di Braccio M, Diomede L, Piccardi N, Cagnotto A, et al. 1,5-Benzodiazepine tricyclic derivatives exerting anti-inflammatory effects in mice by inhibiting interleukin-6 and prostaglandinE(2)production. Pharmacol Res 2001;43(3):445-52.

6. Tardibono LP, Miller MJ. Synthesis and anticancer activity of new hydroxamic acid containing 1,4-benzodiazepines. Org Lett 2009; 11(7):1575-8.

7. Lingjaerde O. Effect of the benzodiazepine derivative estazolam in patients with auditory hallucinations. A multicentre double-blind, cross-over study. Acta Psychiatr Scand 1982;65(5):339-54.

8. Nowakowska Z. A review of anti-infective and anti-inflammatory chalcones. Eur J Med Chem 2007;42(2):125-37.

9. Hans RH, Guantai EM, Lategan C, Smith PJ, Wan B, Franzblau SG, et al. Synthesis, antimalarial and antitubercular activity of acetylenic chalcones. Bioorg Med Chem Lett 2010;20(3): 942-4.

10. Syam S, Abdelwahab SI, Al-Mamary MA, Mohan S. Synthesis of chalcones with anticancer activities. Molecules 2012;17(6):6179-95.

11. Hsieh HK, Tsao LT, Wang JP, Lin CN. Synthesis and anti-inflammatory effect of chalcones. J Pharm Pharmacol 2000; 52(2): 163-71.

12. Bandgar BP, Gawande SS, Bodade RG, Totre JV, Khobragade CN. Synthesis and biological evaluation of simple methoxylated chalcones as anticancer, anti-inflammatory and antioxidant agents. Bioorg Med Chem 2010;18(3):1364-70.

13. Xuan F, Juhua F, Zhenhua D, Lili L, Xiaohua L, Xiaoming F. Enantioselective synthesis of 2-substituted-1,5-benzodiazepines through domino reaction of o-phenylenediamine and chalcone derivatives. Eur JOC 2010;27:5233.

14. Winter CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paws of the rat as an assay for antiiflammatory drugs. Proc Soc Exp Biol Med 1962; 111:544-7.

15. C. A. Winter, E. A. Risley, and G. W. Nuss. Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Experimental Biology and Medicine. 1962; 111(3): 544–547.

16. P. Crunkhorn and S. C. R. Meacock. Mediators of the inflammation induced in the rat paw by carrageenan. British Journal of Pharmacology. 1971; 42(3): 392–402.

17. M. Di Rosa and L. Sorrentino. The mechanism of the inflammatory effect of carrageenan. European Journal of Pharmacology. 1968; 4(3): 340–342.

18. Swarajyam Y. A Study to Assess the Knowledge and Practices of Mothers Regarding Worm Infestation among School age Children (6-12 Years) in Order to Develop Health Education Pamphlet in a Selected Rural Community, Bangalore. Asian J. Nur. Edu. & Research 1(1): Jan.-March 2011; Page 28-30.

19. P. Balakrishnan. A Comparative study to assess the knowledge and attitude of adolescents (16-18 years) regarding alcoholism and its hazards between selected rural and urban Pre-University College at Bangalore. Asian J. Nur. Edu. & Research 1(1): Jan.-March 2011; Page 31-36.

20. Ganesh. A study to assess the effectiveness of structured-teaching programme on knowledge regarding rheumatic fever among school children between the age group of 14 –15 years in a selected school, Chidambaram. Asian J. Nur. Edu. & Research 2(1): Jan.-March 2012; Page 12-14

21. Sherin A. Hameed, Joyamma Varkey, P. Jayasekhar. Schiff bases and Bicyclic derivatives comprising 1, 3, 4-thiadiazole moiety- A Review on their Pharmacological activities. Asian J. Pharm. Res. 2019; 9(4):299-306.

22. Prajakta P Shinde, Shahu D Khule, Sneha Sonawane, Suvarna Shelke. Analgesic activity and anti-inflammatory activity of methanolic extract of plant Sida cordata in carrageenan-induced paw edema in rats. Asian Journal of Pharmaceutical Research. 2021; 11(3):143-6.

23. Kiran Madhawai, Dinesh Rishipathak, Santosh Chhajed, Sanjay Kshirsagar. Predicting the Anti-Inflammatory Activity of Novel 5-Phenylsulfamoyl-2-(2-Nitroxy) (Acetoxy) Benzoic acid derivatives using 2D and 3D-QSAR (kNN-MFA) Analysis. Asian J. Res. Pharm. Sci. 2017; 7(4): 227-234.

24. Debarshi Kar Mahapatra, Ruchi S. Shivhare, Sayan Dutta Gupta. Anxiolytic activity of some 2, 3-dihydrobenzo[b] [1, 4] oxazepine derivatives synthesized from Murrayanine-Chalcone. Asian J. Res. Pharm. Sci. 2018; 8(1):25-29.

25. Dhananjay Babanrao Deshmukh, Mahesh Ramrao Sherkar. Evaluation of In Vivo Analgesic and Anti-Inflammatory Activity of Ethanolic Extract of Medicinal Plant-Lagenaria siceraria. Asian J. Pharm. Tech. 2019; 9(2):75-78.

26. Sujata S. Sawant, Sangram S. Patil, Hemant S. Kandle, Manohar D. Kengar, Ganesh B. Vambhurkar, Mangesh A. Bhutkar. Development and Characterization of Lornoxicam loaded microsponge gel for Rheumatoid arthritis. Asian J. Pharm. Tech. 2019; 9(3):173-178.

27. Vani Mamillapalli, Ratna Harika Chapala, Tejaswi Komal Sai Sareddu, Latha Sri Kondaveeti, Santhi Pattipati, Padmalatha Khantamneni. Evaluation of Phytochemical and in Vitro Anti-Inflammatory activity of Leaf and Fruit Extracts of Casuarina equisetifolia. Asian J. Pharm. Tech. 2020; 10(3):143-148.

Received on 04.09.2021 Modified on 16.11.2021

Asian J. Research Chem. 2022; 15(2):109-114.

DOI: 10.52711/0974-4150.2022.00017