Synthesis and Evaluation of some Novel Triazolo-thiadizoles Derivatives as Anti-diabetic Activity
Amol S. Dighe1,2*, Ashim K. Sen3
1PhD. Scholar, Department of Pharmacy, Sumandeep Vidyapeeth Deemed University,
Pipariya, Vadodara, Gujarat State, India.
2Assistant Professor, Department of Pharmaceutical Chemistry,
Pravara Rural College of Pharmacy, Loni (413736), MH, India.
3Professor, Department of Pharmacy, Sumandeep Vidyapeeth Deemed University,
Pipariya, Vadodara, Gujarat State, India.
*Corresponding Author E-mail: amoldighe143@gmail.com, ashims01@gmail.com
ABSTRACT:
Triazolo-thiodiazole and related fused heterocyclic compounds are of interest as potential bioactive molecules. Triazolo-thiodiazole derivatives have attracted the attention of organic chemists due to their biological and chemotherapeutic significance. Research in the field of anti-mycobacterium, anti-inflammatory and anti-microbial therapies is ongoing and studies are seeking. Therefore, the discovery of new effective anti-mycobacterium, anti-inflammatory and antimicrobial agents is imperative. The literature survey indicates that the fuse ring of triazolo-thiazazole derivatives has proven to be a good bioactive molecule. They showed various biological activities such as antibacterial, antifungal, anti-inflammatory, tubercular, anticancer, anticonvulsant, antioxidant, analgesic. In view of the above facts it was felt that some were interested in triazo- synthesis. All drugs were screened for their anti-diabetic activity with the standard drug Acarbose by an in vitro alpha-amylation method. The compounds C1 and C3 have been shown to have significant anti-diabetic activity.
KEYWORDS: Triazolo-thiodizole, Antibacterial, Anti-diabetic, Antitubercular, Anti-inflammatory.
INTRODUCTION:
There has been much effort in the design and development of the novel triazolo-thiodizole drugs from synthetic origin. Therefore, there is a growing interest in drug potential. Triazolo-thiodiazole compounds are of interest as potential bioactive molecules. Triazolo-thiodiazole derivatives have attracted the attention of organic chemists due to their biological and chemotherapeutic significance1. In many cases, the heterogeneous combination of the ring leads to extensive biological activity in the compounds. Some of the activities performed by asymmetric-tripolo-thiodiazole include antibacterial, anti-inflammatory, anti-diabetic and tubercular2.
Process Pharmacology is primarily concerned with the biological, analytical and biochemical aspects of the process, but the chemist must have productive interactions with those in other disciplines.The process of inventing new drugs is complex and involves the talents of people from different fields such as chemistry, biochemistry, molecology biology, physiology, pharmacy, pharmacology and pharmacology.Therefore, chemist holds a strategic position at the interface of chemistry and biology.3-4
METHOD:
Completes the practical work of the subject
1. Preparation of 2-amino-5-aryl-1, 3, 4-thiadizole (I).
2. Preparation of substituted 5-phenyl-N - [(1Z) -phenylmethylene] -1, 3, 4-thiadiazol-2 Amin (II).
3. Preparation of 2, 5 substituted Triazolo-thiadiazole (III).
1. Preparation of 2-amino-5-aryl-1, 3, 4-thiadizole(I)5
A mixture of thiosemicarbazide (0.1mole), aryl carboxylic acid (benzoic acid, 4-chloro benzoic acid) (0.1 mole), and hides. Sulfuric acid (10 drops) was refluxed for 1 hour. And was poured over crushed ice. The solidly separated filter was washed with water and re-crystallized from ethanol to give I.
2. Preparation of substituted 5-phenyl-N - [(1Z) -phenylmethylene] -1,3,4-thiadiazol-2-amine (II)6
Add 0.01 mol of 2-amino-5-aryl-1,3,4-thiadizole (I), a mixture of 18 ml water and 2.4 ml. Ak. Release 0.01 mol of NH3 and aldehyde (anisalaldehyde, salicylaseled) with stirring over a period of 30–60 minutes. Stir the mixture for further hours, collect the solid by suction filtration and wash it with water. Recalled from Rectified Spirit.
3. Triazolo-thiadizole (III) in preparation of 2, 5.7
A mixture of imine (II) 0.01 mole and FeCl3.6H2O (0.02 mole) and 0.01 mole of INH / Pyrazinoic acid hydrides was ground at room temperature by pestle and mortar. After complete conversion indicated by TLC. The reaction mixture was dissolve with cold water. The resulting solid was filtered, washed with water, and the raw material was purified by re-crystallizing with methanol.
SCHEME:
Table. 1: List of synthesized compounds with their IUPAC names
|
Comp. Name |
Structure |
IUPAC Name |
M. F |
|
A-1 |
|
3-{5-[1-(4-methylphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C22H17N7O2S |
|
A-2 |
|
3-{5-[1-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C21H15N7O3S |
|
B-1 |
|
3-chloro-5-{5-[1-(4-methylphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C22H16ClN7O2S |
|
B-2 |
|
3-chloro-5-{5-[1-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C21H14ClN7O3S |
|
C-1 |
|
2-hydroxy-5-{5-[1-(4-methylphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C22H17N7O3S |
|
C-2 |
|
2-hydroxy-5-{5-[1-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C21H15N7O4S |
|
D-1 |
|
4-{5-[1-(4-methylphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzene-1,2-dicarboxylic acid |
C23H17N7O4S |
|
D-2 |
|
4-{5-[1-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzene-1,2-dicarboxylic acid |
C22H15N7O5S |
|
E-1 |
|
2,3,4-trihydroxy-5-{5-[1-(4-methylphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C22H17N7O5S |
|
E-2 |
|
2,3,4-trihydroxy-5-{5-[1-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C21H15N7O6S |
|
F-1 |
|
3-{5-[1-(4-methylphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}-5-nitrobenzoic acid |
C22H16N8O4S |
|
F-2 |
|
3-{5-[1-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}-5-nitrobenzoic acid |
C21H14N8O5S |
|
G-1 |
|
methyl 2-hydroxy-5-{5-[1-(4-methylphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoate |
C23H19N7O3S |
|
G-2 |
|
methyl 2-hydroxy-5-{5-[1-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoate |
C22H17N7O4S |
|
H-1 |
|
2-(acetyloxy)-6-{5-[1-(4-methylphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C24H19N7O4S |
|
H-2 |
|
2-(acetyloxy)-6-{5-[1-(2-hydroxyphenyl)-5-(pyrazin-2-yl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1,3,4-thiadiazol-2-yl}benzoic acid |
C23H17N7O5S |
Table .2: Analytical data of synthesized compounds.
|
Comp. |
Mol. Formula |
Mol. Wt. |
M.P 0C |
Rf Value |
Yield % |
Elemental analyses Calculated. (Found) Mass % |
|||||
|
C |
H |
N |
Cl |
O |
S |
||||||
|
A-1 |
C22H17N7O2S |
443.48 |
118 |
0.56 |
86.2 |
59.58 |
3.86 |
22.11 |
… |
7.22 |
7.23 |
|
A-2 |
C21H15N7O3S |
445.45 |
121 |
0.52 |
73.25 |
56.62 |
3.39 |
22.10 |
… |
10.78 |
7.20 |
|
B-1 |
C22H16ClN7O2S |
477.93 |
238 |
0.56 |
95.01 |
55.29 |
3.37 |
20.52 |
7.42 |
6.70 |
6.71 |
|
B-2 |
C21H14ClN7O3S |
479.90 |
252 |
0.66 |
83.23 |
52.56 |
2.94 |
20.43 |
7.39 |
10.0 |
6.68 |
|
C-1 |
C22H17N7O3S |
459.48 |
142 |
0.58 |
72 |
57.51 |
3.73 |
21.34 |
… |
10.45 |
6.98 |
|
C-2 |
C21H15N7O4S |
461.45 |
145 |
0.39 |
75.78 |
54.66 |
3.28 |
21.25 |
… |
13.87 |
6.95 |
|
D-1 |
C23H17N7O4S |
487.49 |
163 |
0.73 |
73.1 |
56.67 |
3.51 |
20.11 |
… |
13.13 |
6.58 |
|
D-2 |
C22H15N7O5S |
489.46 |
158 |
0.65 |
72 |
53.98 |
3.09 |
20.03 |
… |
16.35 |
6.55 |
|
E-1 |
C22H17N7O5S |
491.48 |
252 |
0.72 |
82.6 |
53.76 |
3.49 |
19.95 |
… |
16.28 |
6.52 |
|
E-2 |
C21H15N7O6S |
493.45 |
263 |
0.69 |
76.1 |
51.11 |
3.06 |
19.87 |
… |
19.46 |
6.50 |
|
F-1 |
C22H16N8O4S |
488.48 |
235 |
0.68 |
85 |
54.09 |
3.30 |
22.94 |
… |
13.10 |
6.56 |
|
F-2 |
C21H14N8O5S |
490.45 |
241 |
0.42 |
75.3 |
51.43 |
2.88 |
22.85 |
… |
16.31 |
6.54 |
|
G-1 |
C23H19N7O3S |
473.51 |
265 |
0.56 |
84.5 |
58.34 |
4.04 |
20.71 |
… |
10.14 |
6.77 |
|
G-2 |
C22H17N7O4S |
475.48 |
281 |
0.51 |
79.1 |
55.57 |
3.60 |
20.62 |
… |
13.46 |
6.74 |
|
H-1 |
C24H19N7O4S |
491.52 |
145 |
0.57 |
87.6 |
57.48 |
3.82 |
19.55 |
… |
12.76 |
6.39 |
|
H-2 |
C23H17N7O5S |
493.49 |
143 |
0.75 |
95 |
54.87 |
3.40 |
19.47 |
… |
15.89 |
6.37 |
The combustion analysis of compounds synthesized is within the limits of permissible error. (±0.04)
TLC Solvents for Scheme: Ethyl Acetate: Hexane (1:3)
IAEC APPROVAL : Appoval no 1942/PO/Re/S/17/ CPCSEA/2020/02/16 Dated 28-01-2021
MICROBIOLOGICAL SCREENING:
Anti-diabetic activity:
STZ-induced diabetic animal:
Freshly prepared solution of STZ (Sigma, USA), 35 mg/kg body weight in 0.1 mol/L of cold citrate buffer pH 4.5 was introduced into the overnight fasted animals by a single intra peritoneal injection. The control rat will be administrated with saline. The animals were considered diabetic if the blood glucose level values will be more than 250 mg/dL on the third day after STZ injection.
Table 3.1 Anti-diabetic activity of the synthesized compounds.
BLOOD GLUCOSE LEVEL
|
COMPOUND |
Blood Glucose Level |
||||
|
DAY 1 |
DAY 5 |
DAY 10 |
DAY 15 |
DAY 20 |
|
|
GROUP 1 NORMAL CONTROL |
83.42 ± 2.87 |
80.38 ±3.45 |
81.34 ± 3.72 |
80.16 ± 3.91 |
82.75 ± 3.44 |
|
GROUP 2 NEGATIVE CONTROL (STZ 55 mg/kg) |
287.23± 2.89 |
295.07± 0.77 |
281.86± 1.91 |
312.72± 2.98 |
328.93± 5.02 |
|
GROUP 3 POSITIVE CONTROL (ACARBOSE 150 mg/kg) |
279.6± 2.57 |
271.22± 2.75 |
139.63± 3.19*** |
142.86± 5.45*** |
109.21± 3.96*** |
|
A1 200 mg/kg |
286.25±3.71 |
274.45±0.84 |
287.83±2.25 |
284.45±1.94 |
296.1± 3.19 |
|
A1 400mg/kg |
283.11±4.14 |
285.3±2.02 |
289.96±3.05 |
281.65±1.12 |
304.55±4.02 |
|
A2 200 mg/kg |
279.68± 3.03 |
280.08± 1.09 |
275.7± 2.58 |
283.62± 3.25 |
281.71± 8.05 |
|
A2 400mg/kg |
286.41± 3.14 |
277.98± 1.25 |
280.39± 2.09 |
279.53± 2.79 |
227.38±18.07* |
|
B1 200 mg/kg |
277.88±3.09 |
260.85±1.42 |
245.99±1.75 |
239.38±1.13* |
221.26±6.4* |
|
B1 400mg/kg |
275.79± 3.86 |
257.54± 2.14 |
142.91± 2.12** |
151.53± 5.64*** |
132.21± 7.88*** |
|
B2 200 mg/kg |
281.86± 3.15 |
274.65± 2.11 |
277.77± 3.36 |
270.38± 2.54 |
325.87± 3.21 |
|
B2 400mg/kg |
277.55±5.59 |
271.24±0.89 |
270.54±1.37 |
253.36±2.94* |
201.04±17.13** |
|
C1 200 mg/kg |
278.25±3.71 |
279.45±0.84 |
291.83±2.25 |
289.45±1.94 |
299.1± 3.19 |
|
C1 400mg/kg |
272.68± 3.03 |
270.08± 1.09 |
284.7± 2.58 |
286.62± 3.25 |
289.71± 8.05 |
|
C2 200 mg/kg |
276.25±3.71 |
274.45±0.84 |
277.83±2.25 |
274.45±1.94 |
276.1± 3.19 |
|
C2 400mg/kg |
293.11±4.14 |
295.3±2.02 |
299.96±3.05 |
291.65±1.12 |
304.55±4.02 |
|
D1 200 mg/kg |
279.68± 3.03 |
280.08± 1.09 |
275.7± 2.58 |
283.62± 3.25 |
281.71± 8.05 |
|
D1 400mg/kg |
276.41± 3.14 |
277.98± 1.25 |
280.39± 2.09 |
279.53± 2.79 |
237.38±18.07* |
|
D2 200 mg/kg |
299.68± 3.03 |
293.08± 1.09 |
285.7± 2.58 |
293.62± 3.25 |
293.71± 8.05 |
|
D2 400mg/kg |
296.25±3.71 |
284.45±0.84 |
297.83±2.25 |
294.45±1.94 |
306.1± 3.19 |
|
E1 200 mg/kg |
293.11±4.14 |
295.3±2.02 |
299.96±3.05 |
291.65±1.12 |
314.55±4.02 |
|
E1 400mg/kg |
289.68± 3.03 |
289.08± 1.09 |
285.7± 2.58 |
286.62± 3.25 |
289.71± 8.05 |
|
E2 200 mg/kg |
289.41± 3.14 |
287.98± 1.25 |
289.39± 2.09 |
289.53± 2.79 |
237.38±18.07* |
|
E2 400mg/kg |
287.88±3.09 |
270.85±1.42 |
255.99±1.75 |
240.38±1.13* |
224.26±6.4* |
|
F1 200 mg/kg |
285.3±2.02 |
289.96±3.05 |
260.08± 1.09 |
294.7± 2.58 |
279.53± 2.79 |
|
F1 400mg/kg |
285.79± 3.86 |
267.54± 2.14 |
152.91±2.12** |
153.53± 5.64*** |
122.21± 5.88*** |
|
F2 200 mg/kg |
287.55±5.59 |
271.24±0.89 |
264.45±0.84 |
287.83±2.25 |
274.45±1.94 |
|
F2 400mg/kg |
287.55±5.59 |
271.24±0.89 |
270.54±1.37 |
253.36±2.94* |
201.04±17.13** |
|
G1 200 mg/kg |
276.68± 3.03 |
260.08± 1.09 |
294.7± 2.58 |
286.62± 3.25 |
299.71± 8.05 |
|
G1 400mg/kg |
279.25±3.71 |
264.45±0.84 |
287.83±2.25 |
274.45±1.94 |
286.1± 3.19 |
|
G2 200 mg/kg |
296.11±4.14 |
285.3±2.02 |
289.96±3.05 |
291.65±1.12 |
314.55±4.02 |
|
G2 400mg/kg |
289.68± 3.03 |
270.08± 1.09 |
285.7± 2.58 |
283.62± 3.25 |
291.71± 8.05 |
|
H1 200 mg/kg |
286.41± 3.14 |
267.98± 1.25 |
290.39± 2.09 |
279.53± 2.79 |
227.38±18.07* |
|
H1 400mg/kg |
279.68± 3.03 |
273.08± 1.09 |
285.7± 2.58 |
283.62± 3.25 |
293.71± 8.05 |
|
H2 200 mg/kg |
288.68± 3.03 |
273.08± 1.09 |
2785.7± 2.58 |
273.62± 3.25 |
281.71± 8.05 |
|
H2 400mg/kg |
297.55±5.59 |
271.24±0.89 |
270.54±1.37 |
253.36±2.94* |
201.04±17.13** |
Table 3.2 Anti-diabetic activity of the synthesized compounds.
BODY WEIGHT CHANGES
|
COMPOUND |
Body weight Changes |
||||
|
DAY 1 |
DAY 5 |
DAY 10 |
DAY 15 |
DAY 20 |
|
|
GROUP 1 NORMAL CONTROL |
274.36±5.54 |
271.62±5.3 |
277.43±5.63 |
280.78±5.95 |
285.33±5.01 |
|
GROUP 2 NEGATIVE CONTROL (STZ 55 mg/kg) |
273.89±3.87 |
222.79±5.7 |
230.67±5.85 |
219.42±4.78 |
207.09±4.23 |
|
GROUP 3 POSITIVE CONTROL (ACARBOSE 150 mg/kg) |
277.83±2.5 |
261.59±4.31 |
277.91±3.11** |
285.92±7.75** |
301.89±8.06*** |
|
A1 200 mg/kg |
269.44±3.05 |
236.72±4.8 |
203.25±3.87 |
217.57±2.78 |
221.02±7.61 |
|
A1 400mg/kg |
275.13±4.58 |
247.71±5.07 |
244.36±10.74 |
231.25±10.63 |
227.43±14.34 |
|
A2 200 mg/kg |
269.37±3.19 |
240.29±5.09 |
235.03±3.78 |
219.01±6.54 |
228.46±5.32* |
|
A2 400mg/kg |
265.88±4.84 |
256.49±5.25 |
240.06±6.95 |
246.69±11.97 |
253.67±10.1 |
|
B1 200 mg/kg |
264.13±2.31 |
243.3±3.81 |
251.57±8.86 |
240.37±2.87 |
230.43±4.69 |
|
B1 400mg/kg |
276.22±4.48 |
260.18±5.2 |
269.56±4.01 |
288.87±6.08** |
297.62±6.71*** |
|
B2 200 mg/kg |
264.04±3.64 |
252.76±7.34 |
255.57±8.86 |
249.41±6.16 |
229.07±8.18 |
|
B2 400mg/kg |
269.08±3.95 |
254.02±2.87 |
256.06±6.95 |
268.54±5.37* |
279.15±2.78** |
|
C1 200 mg/kg |
267.44±3.05 |
246.72±4.8 |
243.25±3.87 |
247.57±2.78 |
233.02±7.61 |
|
C1 400mg/kg |
265.13±4.58 |
251.71±5.07 |
250.36±10.74 |
241.25±10.63 |
237.43±14.34 |
|
C2 200 mg/kg |
264.88±4.84 |
266.49±5.25 |
243.06±6.95 |
247.69±11.97 |
254.67±10.1 |
|
C2 400mg/kg |
263.13±2.31 |
253.3±3.81 |
252.57±8.86 |
241.37±2.87 |
233.43±4.69 |
|
D1 200 mg/kg |
267.88±4.84 |
268.49±5.25 |
242.06±6.95 |
249.69±11.97 |
256.67±10.1 |
|
D1 400mg/kg |
266.22±4.48 |
263.18±5.2 |
270.56±4.01 |
289.87±6.08** |
298.62±6.71*** |
|
D2 200 mg/kg |
285.13±4.58 |
257.71±5.07 |
254.36±10.74 |
241.25±10.63 |
237.43±14.34 |
|
D2 400mg/kg |
270.37±3.19 |
242.29±5.09 |
236.03±3.78 |
220.01±6.54 |
229.46±5.32* |
|
E1 200 mg/kg |
268.88±4.84 |
258.49±5.25 |
243.06±6.95 |
248.69±11.97 |
255.67±10.1 |
|
E1 400mg/kg |
269.44±3.05 |
238.72±4.8 |
204.25±3.87 |
218.57±2.78 |
222.02±7.61 |
|
E2 200 mg/kg |
274.13±4.58 |
257.71±5.07 |
245.36±10.74 |
230.25±10.63 |
226.43±14.34 |
|
E2 400mg/kg |
268.37±3.19 |
241.29±5.09 |
245.03±3.78 |
229.01±6.54 |
227.46±5.32* |
|
F1 200 mg/kg |
264.88±4.84 |
255.49±5.25 |
239.06±6.95 |
244.69±11.97 |
260.67±10.1 |
|
F1 400mg/kg |
263.13±2.31 |
253.3±3.81 |
253.57±8.86 |
242.37±2.87 |
233.43±4.69 |
|
F2 200 mg/kg |
268.44±3.05 |
244.72±4.8 |
243.25±3.87 |
247.57±2.78 |
232.02±7.61 |
|
F2 400mg/kg |
273.22±4.48 |
262.18±5.2 |
270.56±4.01 |
289.87±6.08** |
298.62±6.71*** |
|
G1 200 mg/kg |
263.88±4.84 |
265.49±5.25 |
242.06±6.95 |
247.69±11.97 |
253.67±10.1 |
|
G1 400mg/kg |
268.08±3.95 |
254.02±2.87 |
255.06±6.95 |
269.54±5.37* |
269.15±2.78** |
|
G2 200 mg/kg |
265.13±4.58 |
251.71±5.07 |
250.36±10.74 |
241.25±10.63 |
237.43±14.34 |
|
G2 400mg/kg |
264.88±4.84 |
266.49±5.25 |
243.06±6.95 |
247.69±11.97 |
254.67±10.1 |
|
H1 200 mg/kg |
263.13±2.31 |
253.3±3.81 |
252.57±8.86 |
241.37±2.87 |
233.43±4.69 |
|
H1 400mg/kg |
268.22±4.48 |
261.18±5.2 |
271.56±4.01 |
288.87±6.08** |
299.62±6.71*** |
|
H2 200 mg/kg |
238.72±4.8 |
243.06±6.95 |
253.76±7.34 |
265.04±3.64 |
264.88±4.84 |
|
H2 400mg/kg |
267.71±5.07 |
252.57±8.86 |
254.02±2.87 |
268.08±3.95 |
263.13±2.31 |
Table 3.3 Anti-diabetic activity of the synthesized compounds.
INSULIN LEVEL
|
COMPOUND |
Insulin Level |
COMPOUND |
Insulin Level |
||
|
DAY 1 |
DAY 20 |
DAY 1 |
DAY 20 |
||
|
GROUP 1 NORMAL CONTROL |
17.21±0.22 |
17.25±0.11 |
GROUP 1 NORMAL CONTROL |
17.21±0.22 |
17.25±0.11 |
|
GROUP 2 NEGATIVE CONTROL (STZ 55 mg/kg) |
7.76±0.17 |
7.75±0.25 |
GROUP 2 NEGATIVE CONTROL (STZ 55 mg/kg) |
7.76±0.17 |
7.75±0.25 |
|
GROUP 3 POSITIVE CONTROL (ACARBOSE 150 mg/kg) |
7.65±0.37 |
13.98±0.37 |
GROUP 3 POSITIVE CONTROL (ACARBOSE 150 mg/kg) |
7.65±0.37 |
13.98±0.37 |
|
A1 200 mg/kg |
7.39±0.37 |
8.19±0.37 |
E1 200 mg/kg |
7.45±0.1 |
8.01±0.29 |
|
A1 400mg/kg |
7.12±0.28 |
8.11±0.28 |
E1 400mg/kg |
7.08±0.34 |
11.07±0.32** |
|
A2 200 mg/kg |
7.46±0.1 |
7.97±0.1 |
E2 200 mg/kg |
7.17±0.36 |
8.05±0.29 |
|
A2 400mg/kg |
7.06±0.34 |
9.78±0.34* |
E2 400mg/kg |
7.38±0.31 |
7.17±0.32 |
|
B1 200 mg/kg |
7.17±0.36 |
8.07±0.36 |
F1 200 mg/kg |
7.06±0.34 |
7.98±0.1 |
|
B1 400mg/kg |
7.38±0.31 |
14.16±0.31*** |
F1 400mg/kg |
7.17±0.36 |
9.79±0.34* |
|
B2 200 mg/kg |
7.24±0.29 |
8.01±0.29 |
F2 200 mg/kg |
7.38±0.31 |
11.07±0.32** |
|
B2 400mg/kg |
7.07±0.32 |
11.07±0.32** |
F2 400mg/kg |
7.24±0.29 |
8.05±0.29 |
|
C1 200 mg/kg |
7.09±0.29 |
8.05±0.29 |
G1 200 mg/kg |
7.08±0.32 |
8.05±0.29 |
|
C1 400mg/kg |
7.31±0.32 |
7.18±0.32 |
G1 400mg/kg |
7.09±0.29 |
9.80±0.34* |
|
C2 200 mg/kg |
7.24±0.29 |
8.20±0.37 |
G2 200 mg/kg |
7.31±0.32 |
8.07±0.36 |
|
C2 400mg/kg |
7.07±0.32 |
8.12±0.28 |
G2 400mg/kg |
7.32±0.37 |
13.16±0.31*** |
|
D1 200 mg/kg |
7.09±0.29 |
7.98±0.1 |
H1 200 mg/kg |
7.13±0.28 |
8.05±0.29 |
|
D1 400mg/kg |
7.31±0.32 |
9.79±0.34* |
H1 400mg/kg |
7.46±0.1 |
7.18±0.32 |
|
D2 200 mg/kg |
7.40±0.37 |
8.07±0.36 |
H2 200 mg/kg |
7.09±0.29 |
8.20±0.37 |
|
D2 400mg/kg |
7.13±0.28 |
14.16±0.31*** |
H2 400mg/kg |
7.31±0.32 |
8.12±0.28 |
Table 3.4 Anti-diabetic activity of the synthesized compounds.
URINE VOLUME
|
COMPOUND |
Urine Volume |
||||
|
DAY 1 |
DAY 5 |
DAY 10 |
DAY 15 |
DAY 20 |
|
|
GROUP 1 NORMAL CONTROL |
1.10±0.14 |
1.40±0.11 |
1.45±0.13 |
1.50±0.2 |
1.45±0.13 |
|
GROUP 2 NEGATIVE CONTROL (STZ 55 mg/kg) |
7.15±0.24 |
8.15±0.44 |
9.75±0.69 |
9.50±0.39 |
10.30±0.06 |
|
GROUP 3 POSITIVE CONTROL (ACARBOSE 150 mg/kg) |
6.65±0.39 |
4.50±0.44 |
5.45±0.63 |
6.70±0.15 |
5.50±0.22 |
|
A1 200 mg/kg |
7.50±0.2 |
7.55±0.36 |
7.30±0.34 |
7.20±0.36 |
8.70±0.44 |
|
A1 400mg/kg |
7.80±0.42 |
6.70±0.64 |
6.50±0.65 |
7.50±0.31 |
8.50±0.63 |
|
A2 200 mg/kg |
6.60±0.47 |
7.30±0.35 |
7.2±0.27 |
7.77±0.44 |
8.75±0.42 |
|
A2 400mg/kg |
7.55±0.41 |
6.45±0.56 |
7.1±0.44 |
7.60±0.6 |
7.10±0.67* |
|
B1 200 mg/kg |
7.50±0.34 |
7.30±0.28 |
6.10±0.2 |
7.50±0.43 |
8.00±0.36 |
|
B1 400mg/kg |
7.20±0.49 |
8.10±0.76 |
6.20±0.71 |
6.60±0.6** |
5.90±0.4*** |
|
B2 200 mg/kg |
7.1±0.45 |
6.8±0.18 |
6.63±0.49 |
7.05±0.63 |
8.05±0.46 |
|
B2 400mg/kg |
7.30±0.55 |
5.20±0.56 |
5.80±0.61 |
6.60±0.51 |
6.50±0.36** |
|
C1 200 mg/kg |
7.40±0.2 |
7.20±0.36 |
7.40±0.34 |
7.30±0.36 |
7.90±0.44 |
|
C1 400mg/kg |
7.10±0.42 |
7.1±0.44 |
6.70±0.65 |
7.30±0.31 |
8.20±0.63 |
|
C2 200 mg/kg |
7.30±0.34 |
7.30±0.28 |
7.80±0.42 |
7.20±0.36 |
8.75±0.42 |
|
C2 400mg/kg |
6.50±0.65 |
6.10±0.2 |
6.60±0.47 |
7.50±0.31 |
7.10±0.67* |
|
D1 200 mg/kg |
7.2±0.27 |
6.20±0.71 |
7.55±0.41 |
7.77±0.44 |
7.30±0.31 |
|
D1 400mg/kg |
7.1±0.44 |
5.80±0.61 |
7.50±0.34 |
7.60±0.6 |
7.20±0.36 |
|
D2 200 mg/kg |
6.10±0.2 |
7.40±0.34 |
7.80±0.42 |
7.50±0.43 |
7.50±0.31 |
|
D2 400mg/kg |
7.30±0.55 |
6.70±0.65 |
6.60±0.47 |
7.20±0.36 |
7.77±0.44 |
|
E1 200 mg/kg |
7.40±0.2 |
7.80±0.42 |
7.55±0.41 |
7.50±0.31 |
7.60±0.6 |
|
E1 400mg/kg |
7.10±0.42 |
6.60±0.47 |
7.50±0.34 |
7.77±0.44 |
6.60±0.47 |
|
E2 200 mg/kg |
7.30±0.34 |
7.55±0.41 |
7.20±0.49 |
7.60±0.6 |
8.00±0.36 |
|
E2 400mg/kg |
6.50±0.65 |
7.80±0.42 |
7.1±0.45 |
7.50±0.43 |
5.90±0.4*** |
|
F1 200 mg/kg |
7.2±0.27 |
7.80±0.42 |
7.55±0.41 |
6.60±0.6** |
8.05±0.46 |
|
F1 400mg/kg |
6.60±0.47 |
7.30±0.34 |
7.30±0.28 |
7.80±0.42 |
6.50±0.36** |
|
F2 200 mg/kg |
7.55±0.41 |
6.50±0.65 |
6.10±0.2 |
6.60±0.47 |
7.90±0.44 |
|
F2 400mg/kg |
7.50±0.34 |
7.2±0.27 |
6.20±0.71 |
7.55±0.41 |
8.20±0.63 |
|
G1 200 mg/kg |
6.10±0.2 |
7.1±0.44 |
5.80±0.61 |
7.50±0.34 |
7.80±0.42 |
|
G1 400mg/kg |
6.20±0.71 |
7.80±0.42 |
7.55±0.41 |
7.55±0.41 |
6.60±0.47 |
|
G2 200 mg/kg |
5.80±0.61 |
6.20±0.71 |
7.55±0.41 |
7.77±0.44 |
7.55±0.41 |
|
G2 400mg/kg |
7.40±0.34 |
6.10±0.2 |
7.77±0.44 |
7.30±0.31 |
7.53±0.34 |
|
H1 200 mg/kg |
6.70±0.65 |
6.20±0.71 |
7.60±0.6 |
7.20±0.36 |
7.81±0.42 |
|
H1 400mg/kg |
7.80±0.42 |
5.80±0.61 |
7.50±0.43 |
7.50±0.31 |
6.61±0.47 |
|
H2 200 mg/kg |
6.10±0.2 |
7.1±0.44 |
5.80±0.61 |
7.50±0.34 |
7.80±0.42 |
|
H2 400mg/kg |
7.77±0.44 |
7.40±0.34 |
6.60±0.6** |
7.77±0.44 |
7.54±0.41 |
Average =ROUND (AVERAGE (A2:A7), 2)
Standard Deviation =ROUND (STDEV (A2:A7), 2)
Standard Error Mean =ROUND (A10/COUNT (A2:A7) ^0.5, 2)
Data was statistically analyzed by One way ANOVA followed by Dennett’s ‘t’ test ,*P<0.01, **P<0.001, *P<0.0001, more Significant Compounds in order B1 400 Dose, F1400 Dose, F2 400 Dose, H2400 Dose, A2 400 Dose, B1 200 Dose, B2 400 Dose, D1 400 Dose and E2 200 Dose, E2 400 Dose , have shown promising anti-diabetic activity. Acarbose was used as standard drug.
RESULT:
The Proposed Compounds Were Screened For their
Anti-Diabetic With The Standard Drugs In The Well-Equipped Microbiology And
Analytical Lab By Using Standard Methods. all drugs were screened for their
anti-
diabetic activity with the standard drug. Acarbose STZ-induced diabetic animal method. The compounds B1, D2 and F1 have been shown to have significant anti-diabetic activity.
DISCUSSION:
Here we have synthesized novel Triazolo-Thiadiazoles and screened them for their antidiabetic activities. The Discussion part mainly deals with the about the synthesized compounds against the antibacterial activity. The compounds A1 and A3 have shown good anti-diabetic activity due to the presence of electron donating groups like –S-,-NH, -OCH3, OH group which is attached to Phenyl and Triazolo-Thiadiazolering system.
CONCLUSION:
The present work is a bonafide and novel for the synthesis of derivatives of 2, 5 substituted triazolothiadiazole.With appropriate modification these compounds can be better explored for their therapeutic activities in the future. Promising biological activities of these compounds are taken into account for drug development and drug discovery Toxicological studies of these compounds will be carried out in the future and effective therapeutic index.
LIST OF ABBREVIATIONS:
INH : Isoniazide
DMF : Dimethyl formamide
DMSO : Dimethylsulfoxide
MW : Microwave
PPA : Polyphosphoric acid
ACKNOWLEDGEMENT:
My special thanks to the Pravara Rural College of Pharmacy, Pravarnagar and Department of Pharmacy, Sumandeep Vidyapeeth Deemed University, Pipariya, Vadodara, for providing the infrastructure and facilities for this research work. I am also grateful to my loving parents and all family members who have been the driving force behind progress and success in every step of my life.
CONFLICT OF INTEREST:
The authors declare no conflict of interest.
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Received on 02.09.2020 Modified on 19.12.2021
Accepted on 28.07.2022 © RJPT All right reserved
Research J. Pharm. and Tech 2023; 16(1):1-7.
DOI: 10.52711/0974-360X.2023.00001