Vasudeva Rao et al, JGTPS, 2014, Vol. 5(3): 1811 -18121811

Dr. A. Vasudeva Rao*3Pharmaceutical Chemistry Division, Sri Venkateswara College

of Pharmacy, Etcherla, Srikakulam-532 410, AP.E-mail: vasudevaraoavupati@rediffmail.com

Address for correspondence

Vasudeva Rao et al / JGTPS/ 5(3)-(2014) 1811-1812

IN VITRO PHARMACOLOGICAL EVALUATION OF (Z)-5-(4-((E)-3-(PHENYL)-3-OXOPROP-1-ENYL) BENZYLIDENE)-1, 3-THIAZOLIDINE-2, 4-DIONE

AS POTENIAL Α-GLUCOSIDASE INHIBITOR

INTRODUCTION Enzyme alpha-glucosidase (EC 3.2.1.20)

catalyzes the final step in the digestive process of carbohydrates; present in the epithelial mucosa of small intestine cleaves glycosidic bonds in complex carbohydrate to release absorbable monosaccharides [1-3]. Inhibition of alpha-glucosidase in the digestive tract delay carbohydrate digestion and prolong overall carbohydrate digestion time, causing a reduction in the rate of glucose absorption and consequently blunting the postprandial blood glucose and insulin levels. Thus alpha-glucosidase inhibitors may be an attractive therapeutic modality in type 2 diabetic patients [4-6]. In the recent past 2,4-thiazolidinediones (TZDs) captivated remarkableimportance as these compounds have been found to exhibit several biological activities, such as antihyperglycemic, euglycemic, anti-inflammatory, antimalarial, antioxidant, antitumor, cytotoxic, antimicrobial, antiproliferative, PPARγ agonist, dual PPARγ/α activator, free radical scavenger, LDL oxidation inhibitor, glycogen synthase kinase (GSK) 3 inhibitor, aldose reductase inhibitor, respectively [7-10].

As a part of our ongoing research in systematic investigation for identifying some novel bioactivecompounds in relation to their α-glucosidase inhibitory activity, we have selected (Z)-5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione. The chemical synthesis and characterization of this compound was earlier reported by one of the author Dr. A. Vasudeva Rao et al [11]. and the novelty of this work is, to date, no reports were available on the α-glucosidase inhibitory activity on this compound.EXPERIMENTALChemical synthesis

The compound (Z)-5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione(1) was procured from Pharmaceutical Chemistry Research Labs, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, as gift sample.

Figure 1: Chemical structure of (Z)-5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-

dione (1)

In the present study a 2,4-thiazolidinedione derivative (Z)-5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione (1) has been studied for its α-glucosidase inhibitory potential. The results clearly state that this compound is a potent inhibitor of α-glucosidase enzyme. This observation is remarkable starting point to develop potential inhibitors of α-glucosidase enzyme.

Keywords: 2, 4-Thiazolidinedione, Alpha-glucosidase (α-glucosidase)

ABSTRACTPrasanth Damarasingu1

Esmaeil Mujavar2

Dr. A. Vasudeva Rao3*

Budumuru Padmasri4

1Pharmacology Research Laboratories, Sri Venkateswara College of Pharmacy,

Etcherla, Srikakulam-532 410, AP, INDIA

2Pharmaceutical Chemistry Division, Andhra University College of

Pharmaceutical Sciences, Visakhapatnam-530 003, AP, INDIA

3Pharmaceutical Chemistry Division, Sri Venkateswara College of Pharmacy, Etcherla, Srikakulam-532 410, AP.

4Pharmaceutical Technology Division, Sri Venkateswara College of Pharmacy,

Etcherla, Srikakulam-532 410, AP.

Journal of Global Trends in Pharmaceutical Sciences

Journal home page: www.jgtps.com

ISSN: 2230-7346

(Research Article)

Vasudeva Rao et al, JGTPS, 2014, Vol. 5(3): 1811 -18121812

Enzyme α-glucosidase inhibition assayThe α-glucosidase inhibitory potential of the (Z)-

5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione (1) was determined by α-glucosidase inhibition assay as described by Pierre et al[12]. α-Glucosidase activity was assayed using 50 mM phosphate buffer at pH = 7.0, and the appropriate PNP (p-nitrophenyl) glycoside (at 1 mM) were used as substrates. The concentration of the enzyme was specified in each experiment. (Z)-5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione (1) at the designated concentration was added to the enzyme solution and incubated at 37 °C for 30 min, and the substrate was then added to initiate the enzyme reaction. The enzyme reaction was carried out at 37 °C for 30 min. Product (PNP) was monitored spectrophotometrically by measuring the absorbance (λ = 400 nm). One unit of α-glucosidase is defined as the amount of enzyme liberating 1.0 μmol of PNP per minute under the assay conditions specified. The enzyme reaction was performed in the above reaction conditions with inhibitors of various concentrations. Inhibition types for the inhibitors were determined by Lineweaver–Burk plots and its replot of slope versus the reciprocal of the substrate concentration. The characterization of secondary structure of α-glucosidase in the buffer solution with or without inhibitors was examined with CD spectroscopy. The data obtained from the experiments were dealt with the professional software secondary structure estimation and Origin 6.0. The result for the test compound was compared with the positive control Acarbose [12].

RESULTS AND DISCUSSIONChemical synthesis

The chemical synthesis, physical and spectroscopic characterization of the selected compound (Z)-5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione (1) was earlier reported by one of the authors Dr. A. Vasudeva Rao et al.[11]

Enzyme α-glucosidase inhibition assayFrom the analysis of in vitro α-glucosidase

inhibitory activity screening data discovered that the compound (Z)-5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione (1)

demonstrated comparatively the most effective inhibitory activity, with IC50 values of 17.33 ± 0.22 µg/mL in comparison with the standard drug (Acarbose, IC50 : 0.027 ± 0.27 µg/mL). The α-glucosidase inhibitory activity is significantly affected by substituents at position 1and 3 of α,β-unsaturatedketone system.

CONCLUSION In conclusion we could evaluate the α-

glucosidase inhibitory potential of (Z)-5-(4-((E)-3-(phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione (1) and it was appeared to be a good inhibitor of α-glucosidase enzyme.

REFERENCES 1. Fujisawa, T.; Ikegami, H.; Inoue, K.; Kawabata,

Y.; Ogihara, T. Metabolism. 2005, 54, 387-390. 2. Sou, S.; Takahashi, H.; Yamasaki, R.; Kagechika,

H.; Endo, Y.; Hashimoto, Y. Chem. Pharm. Bull. 2001, 49, 791-793.

3. Liu, Y.; Zou, L.; Ma, L.; Chen, W. H.; Wang, B.; Xu, Z. L. Bioorgan. Med. Chem. 2006, 14, 5683-5690.

4. Pandey, J.; Dwivedi, N.; Singh, N.; Srivastava, A. K.; Tamarkarb, A.; Tripathi, R. P. Bioorg. Med. Chem. Lett. 2007, 17, 1321-1325.

5. Look, G. C.; Fotsh, C. H.; Wong, C. H. Acc. Chem. Res. 1993, 26, 182-190.

6. Roth, J.; Ziak, M.; Zuber, C. Biochimie. 2003, 85, 287-294.

7. Kaushal, G. P.; Pastuszak, I.; Hatanaka, K. I.; Elbein, A. D. J. Biol. Chem. 1990, 265, 16271-16279.

8. Hammond, C.; Braakman, I.; Helenius, A. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 913-917.

9. Alonso, J. M.; Santa-Cecilia, A.; Calvo, P. Eur. J. Biochem. 1993, 215, 37-42.

10. Takeda, Y.; Totoni, K.; Matsuo, I.; Ito, Y. Bioorg. Med. Chem. Lett. 2010, 20, 5357-5359.

11. Vasudeva Rao, A.; Rajendra Prasad, Y.; Annapurna, Akula.; Girija Sankar, G.; Bhagya Raju, D.; Venkata Rao, V.; Suvarna Ratna, A.; Lakshmana Santhi, A.; Aruna Kumar, V. Bioorg. Med. Chem. Lett. 2012, 22, 6442-6450.

12. Pierre, C.; Roland, R.; Tremblay, D. J. Clin. Chem. 1978, 24, 208–211.

How to cite this article: Prasanth Damarasingu, Esmaeil Mujavar, Dr. A. Vasudeva Rao*, Budumuru Padmasri: In Vitro Pharmacological

evaluation of (Z)-5-(4-((E)-3-(Phenyl)-3-Oxoprop-1-Enyl) Benzylidene)-1, 3-Thiazolidine-2, 4-Dione as potenial Α-Glucosidase Inhibitor: 5(3): 1811-12. (2014)

All © 20104 are reserved by Journal of Global Trends in Pharmaceutical Sciences.