The Hypoglycemic and Hypolipidemic Effect of 5- Naphthalidin-2, 4 Thiazolidinedione derivatives in Alloxan Induced Type II Diabetic Model


Rekha. S1*, Kalpana Divekar2, Chandrashekhara. S3

1Department of Pharmaceutical Chemistry, College of Pharmaceutical Sciences,

Dayananda Sagar University, Bangalore, Karnataka, India.

2Department of Pharmaceutical Chemistry, College of Pharmaceutical Sciences,

Dayananda Sagar University, Bangalore, Karnataka, India.

3Department of Pharmaceutics, Dr. Ravi Patil College of Pharmacy, Belgaum, Karnataka, India.

*Corresponding Author E-mail:



Objective: The present study was undertaken to study antidiabetic and antihyperlipidemic potentials of 5- naphthalidin-2, 4-thiazolidinediones derivatives and its interaction with rosiglitazone in alloxan-induced diabetic rats. Methods: Diabetes was induced in male swiss albino rats by single intramuscular injection of alloxan (0.15 mg/Kg i.m) and NIDDM-rats received 4b, 4c or 4d (36 mg/Kg, p.o). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by Duncan's Multiple Range Test (DMRT). Results: The results revealed that 4b, 4c and 4d showed promising results by lowering the blood glucose. Moreover, 4c compound displayed high efficiency for lowering lipid profiles compared to others. Conclusion: These results suggest that taking 5- naphthalidin-2, 4 TZD orally twice/day is a valuable treatment for Non insulin dependent diabetes mellitus (NIDDM) and hypolipidemic agent. They exert their effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats.


KEYWORDS: Diabetes, Free radical scavenging activity, RIN-5F cells, Diseased human lung fibroblast.




Diabetes mellitus (DM) is a multifarious or polygenic disorder, which is characterized by abnormal increase levels of glucose (hyperglycemia) and deficiency in insulin secretion leading to type II diabetes mellitus known as NIDDM or resistance to insulin over an elongated period in the liver and peripheral tissues leading to type I DM i.e., Insulin dependent diabetes mellitus (IDDM).1


Hyper-triglyceridemia is the major metabolic syndrome associated with diabetes. The increased level of triglycerides leads to acute pancreatitis along with other lipid abnormalities such as hypercholesterolemia, cardiovascular diseases, and obesity 2. Diabetes, most of the time associated with lipid abnormalities in the body with reduced high-density lipoprotein (HDL) and raised low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides (TG) levels3.


Thiazolidine-2, 4-dione (TZD) is a peroxisome proliferator activated receptor (PPARγ) agonist which is a privileged scaffold and an excellent heterocyclic moiety in the field of drug discovery of antidiabetic drugs. This stimulates peripheral adiposities to promote adipogenesis and uptake of free fatty acids (in peripheral but not visceral fat), which leads to reduction in the fat storage4.

In this research, we investigated the insulinotropic effect of 5-substituted 2,4 TZD with standard reference rosiglitazone in-vivo, which included the dose and time dependent stimulation of β pancreatic cells to release insulin in insulin-sensitive tissues5.


The new drugs synthesised also displayed high efficiency in increasing HDL level and also HDL/LDL ratio, which provide useful results for the interpretation of hypolipidemic activity.



Drugs and Chemicals:

Alloxan procured from Sigma, St. Louis, MO, USA. Ascorbic Acid-Qualigens, Methanol-Qualigens was of the highest analytical grade available.



Rosiglitazone is an oral hypoglycemic drug in the thiazolidinedione class of drugs. It acts as PPAR gamma receptors agonist 6.


Chemical Kit:

1.     Chem Kit for Glucose estimation: Span diagnostics Ltd, Surat, India

2.     Chem. Kit for Cholesterol estimation: Coral clinical systems, Verna Goa, India

3.     Chem. Kit for Triglycerides estimation: Coral clinical systems, Verna Goa, India

4.     Commerical Kit for HDL-C and LDL-C estimation: Dialab, Austria.


Synthesis of 2-Imino-4-thiazolidinedione:

Synthesis of 2-imino-4-thiazolidinedione was carried out by taking equimolar quantities of 2-chloroethylacetate (104 Moles) with thiourea (96 Moles) and dissolved in ethanol and refluxed over a period of 3hr. The mixture was cooled to room temperature. The HCl salt which formed was added to water and neutralized with solution of sodium acetate, which precipitated 2-imino-4-thiazolidinedione on cooling. The product was filtered and dried at 60oC. TLC solvent system ethylacetate: methanol (1:2).

IR showed absorption at (cm-1): 3074, 3059(-NH, NH-), 1620(-C=O-) and 746(-C-S-C-). M.P = 186 - 1880C.


Synthesis of 2, 4-Thiazolidinedione:

The 2-Imino-4-thiazolidinedione was hydrolyzed with 2N HCl in ethanol by refluxing for 15hr. The reaction mixture cooled was neutralized with saturated solution of NaHCO3 (10%). The crude product 2-4-thiazolidinedione was separated as solid. This was recrystallised from ethanol: water (40:60) mixture. TLC solvent system ethylacetate: methanol (1:2).


Synthesis of 5-[(2-Hydroxy)-naphthylidene]-2,4-thiazolidinedione:

Equimolar amounts of variously substituted aldehydes and 2,4-thiazolidinedione was refluxed in absolute ethanol (till the sample dissolves) for 4hr in the presence of piperidine. The mixture was cooled and poured on to crushed ice with stirring. The product obtained is washed with toluene to give 5-[(2-Hydroxy)- naphthylidene] - 2,4-thiazolidinedione. TLC solvent system used ethylacetate: methanol (1:2).


Synthesis of 5-[(2-Hydroxy)-naphthylidene]-3- (N- Carbamate)-2,4-thiazolidinedione:

5-[(2-Hydroxy)-naphthylidene]-2,4-Thiazolidinedione (0.1mole) and triethylamine (0.15mole) in DMF (150ml) was added methyl chloroformate (0.15mole) dropwise at 0-5ºC. Then, the reaction mixture was refluxed for 15hr in an oil bath. The reaction was continuously monitored by TLC using toluene: ethylacetate (1:1). Later the reaction is poured into dil.HCl (160ml, 50% v/v) with constant stirring. The crude product obtained was filtered, dried and purified by crystallization using absolute alcohol.


Synthesis of 5-[(2-hydroxy)-naphthylidene]-3-(N-semicarbazide)-2,4 thiazolidinedione:

The mixture of 5-[(2-hydroxy)-naphthylidene]-3- (N- carbamate)-2, 4-thiazolidinedione (0.1mole) and hydrazine hydrate (0.43mole) in alcohol (till the sample dissolves) was heated in an oil bath for 18hr. The reaction progress was monitored by TLC using toluene: ethylacetate (1:1). Cooled reaction gives yellow crystals. Re-crystallization by absolute alcohol is done.


Synthesis of 5-[(2-Hydroxy)-naphthylidene]-3-(N-41arylmethyl semicarbazide)-2, 4-thiazolidinedione:

A mixture of 5-[(2-Hydroxy)-naphthylidene]-3-(N-semicarbazide)-2,4-thiazolidine dione (0.01mole), substituted aldehydes (0.012mole) and hydrochloric acid (0.18ml) was refluxed for 4hr. Progress of the reaction was checked by TLC using toluene: ethylacetate (1:1) as eluent. The solid obtained was filtered, dried and crystallized from absolute alcohol to give 5-[(2-Hydroxy)-naphthylidene]-3-(N-41arylmethyl semi-carbazide)-2,4-thiazolidinedione.


General procedure for synthesis of substituted 5-[(2-Hydroxy)-naphthylidene]-3-(N-41arylmethyl semicarbazide)-2, 4-thiazolidinedione (4a-g):

To a continuously stirred mixture of compound 4 (0.35g, 0.00110mol) and appropriate arylidine compounds (0.3g, 0.00110mol) in ethanol (8 mL), few drops of piperidine was added. The reaction mass was refluxed for 6-8 h. The progress of the reaction was continuosly monitored by TLC. After cooling, the separated solid or residue was filtered, washed with hot ethanol. All the compounds were further purified by re-crystallized in ethanol in order to get the desired title compounds (4a-g).


In-vivo and In vitro Screening for Anti-Diabetic Activites:

Animals 7, 8

Male albino rats weighing 150-200g were used for this study. Rats were caged under controlled temperature of 20-240C and maintained on 12 hr light/dark cycle. They were fed with standard laboratory pellets and water ad libitum. For induction of diabetes, rats were kept on fasting prior to alloxan injection (Sigma aldrich) (150 mg/Kg body weight in 0.9% NaCl, pH 4.5) by intraperitoneal route.


The animals were fed with commercially available rat pelleted diet (Sai Durga feeds and foods, Bangalore). Water was allowed ad libitum under strict hygienic conditions. The study protocols were duly approved by the Institutional Animal Ethics Committee (IAEC) of College of Pharmaceutical Sciences, Dayananda Sagar University (DSU/PhD/IAEC/09/2017-18), Bangalore and studies were performed in accordance with the CPCSEA guidelines.


Experimental Design:9-11

In the present investigation, a total of 36 rats (30 diabetic surviving rats and 6 normal rats) were divided into six groups of 6 rats each. Control rats were treated with carboxy methyl cellulose (CMC) alone. The rats with a blood glucose level above 150 mg/dl were considered to be diabetic and used in the experiment for 15day treatment

Group I: Normal control - Received 0.25% CMC p.o and sterile water for injection i.m.

Group II: Alloxan control - Received 0.25% CMC p.o and alloxan 0.15 mg/Kg i.m.

GroupIII: Rosiglitazone treated - Received rosiglitazone 500 μg/Kg body weight i.p.

Group IV: Received 4b, 36 mg/Kg in 0.25% CMC p.o and alloxan 0.15 mg/Kg i.m.

Group V: Received 4c, 36 mg/Kg in 0.25% CMC p.o and alloxan 0.15 mg/Kg i.m.

Group VI: Received 4d, 36 mg/Kg in 0.25% CMC p.o and alloxan 0.15 mg/Kg i.m.


Treatment was continued for 15 days. On day 15, after overnight fasting, blood samples were collected by withdrawing a drop of blood from tail vein by tail tipping method. The blood was dropped on the reagent strip and inserted into the digital blood glucometer and the readings were noted.


Selection of laboratory model:

Animal such as rabbits, rats and Syrian hamsters have been used in experimental study of Hyperlipidemia. In the present study, rats have been used. The hepatic system of rats resembles human hepatic system in characteristics believed to contribute to Hyperlipidemia.


Acute model:12, 13

Triton WR – 1339, a non-ionic detergent (oxy ethylated tertiary octyl phenol formaldehyde polymer), has been widely used to produce “Acute Hyperlipidemia” in animal models in order to screen natural or chemical drugs.


Experimental Design:

Albino rats (Wistar strain) of either sex weighing between 150-200g were procured. The animals were acclimatized for seven days under laboratory conditions. The animals were fed with commercially available rat pelleted diet Studies were performed in accordance with the CPCSEA guidelines.


The experimental group consists of 5 groups of 6 animals each with normal control group, test drug treated groups (4b, 4c and 4d 36mg/kg) and positive control group with standard (Simvastatin 7.2mg/kg). The treated groups, both test group and positive control group were given daily prophylactic dose of the test drugs and Simvastatin 7.2mg/kg respectively for 7 days.


Treatment Protocol:

Group I: Normal control - Received 0.25% CMC p.o and sterile water for injection i.m.

Group II: Hyperlipidemic control Triton WR – 1339 200mg/kg body Weight

Group III: Rosiglitazone treated - Received rosiglitazone 500μg/Kg body weight i.p.

Group IV: Received 4b, 36 mg/Kg in 0.25% CMC p.o and alloxan 0.15mg/Kg i.m.

Group V: Received 4c, 36 mg/Kg in 0.25% CMC p.o and alloxan 0.15mg/Kg i.m.

Group VI: Received 4d, 36 mg/Kg in 0.25% CMC p.o and alloxan 0.15mg/Kg i.m.

Group VII: Simvastatin 7.2mg/kg was given orally (high fat-fed diet, induced with alloxan, diabetic) treated with 10mg/kg bw of rosiglitazone. Daily once for the week.


On seventh day 200mg/kg Triton WR – 1339 was injected i.p to all the groups of rats immediately after drug administration. Blood was collected by retro orbital puncture at the 48 hrs and the serum was separated in cooling centrifuge by centrifuging at 2500rpm for 10 min14.


Biochemical analysis:

The serum was analyzed for total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and using standard protocol methods using semi auto analyzers and chemical kits.


Statistical analysis:

All the results were expressed as mean ± SEM. Data was analyzed by one way analysis of variance (ANOVA) followed by Duncan's Multiple Range Test (DMRT). The p values <0.001 were considered as statistically significant



The body weights of normal and diabetic rats were significantly (p< 0.001) decreased in the alloxan induced diabetic group with comparison to control. The data showed a progress in the body weight after 21 days of supplementation, the animals started to gain their normal weight back as shown in Fig 1.


Administration of 5-naphthalidin-thiazolidinedione derivatives 4b, 4c and 4d in alloxan induced diabetic rats produced a major reduction in serum glucose levels when compared with control are shown in Fig 2.


Hyperlipidemia was induced in rats by injecting Triton WR-1339 at the dose of 200 mg/kg b.w. After injecting triton, levels of TC, TG, HDL and LDL in all the groups were eleveated after 24 and 48 hrs and the results are shown in the Table 4. In Hyperlipidemic group significant elevation was seen in serum total cholesterol (TC) level after 24 and 48 hrs of tritonization. Simultaneously, the triglycerides (TG), HDL and LDL levels also significantly amplified during 48 hrs15.



The structure of new compounds synthesized during present investigation has been authentically established by their UV, FTIR, H1NMR, and C13 NMR.


As shown in the scheme cyclisation of 2-chloro ethyl acetate with thiourea in ethanol to give 2-Imino-thiazolidinedione followed by hydrolysis with HCl to afford 2,4-Thiazolidinedione. On condensation with 2-hydroxynaphthaldehyde in presence of piperidine to form 5-[(2-Hydroxy)-naphthylidene]-2,4-thiazolidinedione which on treatment with methylchloroformate yielded 5-[(2-Hydroxy)-naphthylidene]-3-(N-Carbamate)-2,4-thiazolidinedione. This was followed by condensation with hydrazinehydrate to give 5-[(2-Hydroxy)-naphthylidene]-3-(N-semicarbazide)-2,4-thiazolidinedione. This semicarbazide was transformed into semicarbazones by condensation with substituted aromatic aldehydes to get 5-[(2-Hydroxy)-naphthylidene]-3-(N-41 arylmethyl semicarbazide)-2,4-thiazolidinedione, using this as a parent compound derivatives 4a-e was synthesised16.


The in-vivo oral hypoglycemic activity of 5- naphthylidene TZD derivatives was screened for the prominent action on insulin secretion. The results of this study also demonstrated that 4b, 4c and 4d for 21 days had regenerative potential with increased insulin secretion from β-cells of islets of langerhans of pancreas in Type II diabetic rats as shown in the Fig-2. From the results, it may be suggested that the mechanism of action of 5- naphthylidene TZD may be similar to that of rosiglitazone i.e., standard reference17-20.


The rats treated with 4c TZD derivative indicated significant increase in blood glucose (P < 0.01), serum cholesterol (P < 0.05), triglycerides (P < 0.05) and LDL-C level (P < 0.05) whereas HDL-C level was found to be increased (P < 0.05) as compared with the diabetic control group in both types.



The present findings show that oral administration of 5-naphthylidene 2,4-thiazolidinediones derivatives produces significant decrease in blood glucose levels vowing for anti-diabetic activity. The phenolic moiety present is effective against dyslipidemia, and proved by significant reduction in serum cholesterol, triglycerides and LDL-C levels; at the same time increases HDL-C in alloxan induced type-II diabetic rats.



I sincerely thank Management and Dr. V. Murugan, Dean, College of Pharmaceutical Sciences, Dayananda Sagar University, Kumaraswamylayout, Banagalore for providing me an oppurtunity to embark on this project. I extend my thanks to Dr. Ashutosh Das and Dr. Saravanan, CRD section, PRIST University, Thanjavur for their continuous support.



The authors declared no conflict of interest.



All the authors have equal contribution for the manuscript preparation, and especially edited and the final copy was revised by Dr. Chandrashekhar and Dr. Kalpana Divekar.


Table 1: Physical properties of synthesized compounds



C. C.*


% yield




Yellow orange solid





Pale Yellow solid


235-240 °C



Yellow solid





Yellow solid


220-225 °C



Yellow solid


225-230 °C



Yellow solid


205-215 °C



Yellow solid


215-230 °C



Table 2: Elemental and spectral analysis data of synthesized compounds.

Comp. Code

Elemental Analysis (Calculated)

IR. values (cm-1)


C= 63.31, H= 6.71, N= 7.77, O= 13.32, S= 8.90

3110.17 (N-H Str.), 3050.78 (Ar-H Str.), 2962.89 (C-H Str. of CH3), 1693.70 (C=O Str.), 1600.52 (C=C Str.), 1512.47 (C=N Str.)


C= 59.65, H= 6.12, N= 7.73, O= 17.66, S= 8.85

3009.90 (N-H Str.), 2932.45 (Ar-H Str.), 2835.61 (C-H Str. of CH3), 1720.49 (C=O Str.), 1635 (C=C Str.), 1600.06 (C=N Str.)


C= 61.31, H= 5.71, N= 6.77, O= 11.32, S= 7.90

3120.74 (N-H Str.), 3015.85 (Ar-H Str.), 2964 (C-H Str. of CH3), 1700 (C=O Str.), 1591.59 (C=C Str.), 1515.23 (C=N Str.)


C= 61.31, H= 6.31, N= 7.17, O= 13.12, S= 7.90

3000.21 (N-H Str.), 2950.09 (Ar-H Str.), 2835.81 (C-H Str. of CH3), 1715.41 (C=O Str.), 1628.05 (C=C Str.), 1510.55 (C=N Str.)


C= 59.31, H= 7.71, N= 6.77, O= 11.32, S= 7.90

3075.62 (N-H Str.), 2910.80 (Ar-H Str.), 2850.79 (C-H Str. of CH3), 1718.58 (C=O Str.), 1625.09 (C=C Str.), 1600.95 (C=N Str.)


C= 38.91, H= 3.46, N= 21.96, O= 30.32, S= 25.38

3200.99 (N-H Str.), 3100.46 (Ar-H Str.), 2850.65 (CH Str. of CH3), 1650.41 (C=O Str.), 1600.30 (C=C Str.), 1591.71 (C=N Str.)


C= 60.31; H=1.95; N=20.05; O=24.68; S, 11.38

3317.23 (N-H Str.), 3100.86 (Ar-H Str.), 2900.41 (C-H Str. of CH3), 1700.20 (C=O Str.), 1630.90 (C=C Str.), 1530.99 (C=N Str.)



Table 3: H1NMR and C13NMR data of synthesized compounds 7

Comp. Code

H1NMR (400 MHz, DMSO-d6, δ, ppm)

C13NMR (100 MHz, DMSO, δ ppm)


9.51 (s, 1H, NH), 6.97-6.96 (d, 1H, J = 5.00 Hz), 6.86 (s, 1H, C=C-H), 8.62-7.61 (d, 1H, J = 3.44 Hz), 6.30 (s, 1H, Ar-H), 6.22-7.00 (m, 2H), 6.50-6.75(m, 2H), 2.84 (s, 3H, -OCH3), 2.78 (s, 3H, -OCH3)

166.91 (C=O, thiazolidin-4-one), 162.70 (C=N, 2-ylidene carbon), 160.30 (C=N of thiazolidone), 150.75, 14999, 135.82, 132.59, 133.23, 130.82, 129.87, 127.24, 121.18 (C-H, benzylidene carbon), 121.98 (C-5 of thiazolidone), 56.54 (-OCH3)


11.61 (s, 1H, NH), 7.72-7.71 (d, 2H, J = 5.04 Hz), 6.57-7.56 (d, 2H, J = 5.10 Hz), 6.53 (s, 1H, C=C-H), 6.27 (s, 1H, Ar-H), 6.18-7.17 (d, 1H, J = 8.28 Hz), 5.99-6.25 (d, 1H, J = 8.22 Hz), 2.84 (s, 3H, -OCH3)

166.20 (C=O, thiazolidin-4-one), 165.59 (C=N, 2-ylidene carbon), 157.53 (C=N of thiazolidone), 151.97, 150.71, 140.31, 135.19, 130.51, 130.18 (C-5 of thiazolidone), 125.18 (C-H, benzylidene carbon), 124.70, 62.31, 58.18 (-OCH3)


11.50 (s, 1H, NH), 7.25 (s, 1H, Ar-H), 7.42 (s, 1H, C=C-H), 7.26-7.34 (d, 2H, J = 8.04 Hz), 7.30 (s, 1H, Ar-H), 7.20-7.15 (m, 2H), 6.78-6.82 (m, 2H), 2.84 (s, 3H, -OCH3), 2.31 (s, 3H, -CH3)

168.22 (C=O, thiazolidin-4-one), 164.59 (C=N, 2-ylidene carbon), 157.80 (C=N of thiazolidone), 150.51, 140.24, 137.26, 135.41, 131.88, 130.84 (C-H, benzylidene carbon), 130.80, 128.75, 127.29, 125.06 (C-5 of thiazolidone), 56.47 (-OCH3), 20.04 (-CH3)


11.66 (s, 1H, NH), 8.65 (s, 1H, C=C-H), 7.60-7.59 (d, 1H, J = 3.76 Hz), 7.02-8.01 (d, 1H, J = 7.00 Hz), 6.62 (s, 1H, C=C-H), 6.58-6.55 (dd, 1H, J = 7.89, 4.24 Hz), 628 (s, 1H, Ar-H), 4.83 (s, 3H, -OCH3)

168.85 (C=O, thiazolidin-4-one), 164.93 (C=N, 2-ylidene carbon), 158.39 (C=N of thiazolidone), 152.05, 150.76, 149.96, 138.69, 136.79, 130.81, 138.82, 128.16, 126.70 (C-5 of thiazolidone), 126.30 (C-H, benzylidene carbon), 125.09, 56.47 (-OCH3)


11.54 (s, 1H, NH), 6.68 (s, 1H, C=C-H), 6.56-7.48 (m, 5H, Ar-H), 7.14 (s, 1H, C=C-H), 6.02-7.00 (d, 1H, J = 8.76 Hz), 2.80 (s, 3H, -OCH3)

168.06 (C=O, thiazolidin-4-one), 161.99 (C=N, 2-ylidene carbon), 156.76 (C=N of thiazolidone), 151.12, 149.95, 150.97, 151.87, 134.77, 130.01, 130.50, 129.23, 129.71, 128.01 (C-H, benzylidene carbon), 124.14 (C-5 of thiazolidone), 118.39, 56.43 (-OCH3)


11.43 (s, 1H, NH), 8.55 (s, 1H, C=C-H), 6.44 (s, 1H, C=C-H),6.28 (s, 1H, Ar-H),6.25 (s, 1H, Ar-H), 5.97-5.95 (d, 1H, J = 8.40 Hz),4.13 (s, 3H, -OCH3), 4.00 (s, 3H, -OCH3), 3.82 (s, 3H, -OCH3)

168.25 (C=O, thiazolidin-4-one), 165.88 (C=N, 2-ylidene carbon), 165.16 (C=N of thiazolidone), 149.39, 150.19, 158.95, 125.31, 127.24, 129.88 (C-H,benzylidene carbon), 120.36, 122.55, 124.46, 118.14, 116.03, 58.63 (-OCH3), 54.51 (-OCH3), 56 .47 (-OCH3)


11.88 (s, 1H, NH), 6.70 (s, 1H, C=C-H), 7.08-7.16 (d, 2H, J = 8.34 Hz), 7.44 (s, 1H, C=C-H), 7.25 (s, 1H, Ar-H), 7.18-6.97 (d, 1H, J = 8.28 Hz), 4.09 (s, 3H, -OCH3)

167.42 (C=O, thiazolidin-4-one), 164.13 (C=N, 2-ylidene carbon), 156.62 (C=N of thiazolidone), 150.57, 136.82, 133.56, 132.62, 129.65, 127.94 (C-H, benzylidene carbon), 126.97, 125.04 (C-5 of thiazolidone), 123.41, 79.64, 79.41, 79.19, 56.34 (-OCH3)


Table 4: Changes in serum lipid profiles in normal and diabetic rats after 7 days of treatment with 4b, 4c and 4d TZD derivative.

Experimental group

TC mg/dL

TG mg/dL

HDL mg/dL



52.74 ± 3.15

74.09 ± 2.47




106.77 ± 3.30***a

155.21 ± 2.06***a



Diabetic control






104.15±1.98 ***b





50.74 ± 2.15***b

68.09 ±1.47***b





72.74± 3.15***b




50.74 ± 1.15***b

70.09 ± 2.47***b



Values are expressed as mean ± SEM.

Values were found out by using ONE WAY ANOVA followed by Duncan's Multiple Range Test.

*** (a) values were significantly different from normal control at P< 0.001

*** (b) Values were significantly different from hyper-lipidemic control at P< 0.001


Fig 1: Changes in rats' body weight (g). Each bar represents the mean ± SD of rats. 4b, 4c and 4d and the values were expressed as mean±SD.


Fig 2: Effect of derivatives on blood glucose levels (mg/dl) in alloxan induced insulin resistant model in rats.

Fasting blood glucose level in the 4b, 4c and 4d treated rats, decrease in blood glucose level was prominent from Day 1 onwards; the decrease in blood glucose level was highly pronounced after Day 15. The hypoglycemic effect of 4b, 4c and 4d at 36 mg/kg dose was more prominent than rosiglitazone (the reference standard).



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Received on 01.02.2021            Modified on 28.04.2021

Accepted on 03.06.2021           © RJPT All right reserved

Research J. Pharm.and Tech 2022; 15(4):1505-1511.

DOI: 10.52711/0974-360X.2022.00250