Biological Evaluation of New Oxadiazole-Based Synthetic α-glycosidase Inhibitors for Hyperglycemia Management: A Research Study New Oxadiazoles act as a-glycosidase inhibitor
Iranian Journal of Pharmaceutical Sciences,
Vol. 18 No. 1 (2022),
15 January 2022
,
Page 65-75
https://doi.org/10.22037/ijps.v18.41378
Abstract
The present study was conducted to investigate the hypoglycemic activity of 3,4,5-triphenyl-oxadiazole derivatives and its effects on liver, lung, and kidney function in streptozotocin (STZ)-induced diabetic rats. For this purpose, male Wistar rats were divided into four groups (n = 4). Diabetes was induced in four groups by a single dose of STZ at 65 mg/kg body weight, administrated intraperitoneal. After 28 days of treatment, fasting blood sugar (FBS) levels and other biochemical parameters such as cholesterol, triglycerides phosphorous, urea creatinine, etc. were measured. Also, the markers of liver and kidney function, such as urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase levels were determined. The study showed that the 3,4,5-triphenyl-oxadiazole derivatives at 100 mg/kg body weight had a significant antidiabetic activity after 28 days of treatment as the FBS levels decreased significantly while the serum insulin levels increased. Moreover, a significant decrease in the liver and kidney function markers in treated rats indicated the protective effect of the 3,4,5-triphenyl-oxadiazole derivatives against liver and kidney damage. The serum concentrations were normal in the control and the healthy group treated with these derivatives. The results of this study showed that both derivatives can regulate hyperglycemia and complications of diabetes.
- 3,4,5-triphenyl-oxadiazole derivatives;
- Diabetes mellitus;
- Hyperglycemia;
- Streptozotocin;
- hypoglycemic activity
How to Cite
References
[2] Misra A, Gopalan H, Jayawardena R, P Hill A, Soares A, Reza-Albarrán AA, Ramaiya KL. Diabetes in developing countries. J Diabetes. (2019 ) 11(7):522-539.
[3] Leroux-Stewart J, Rabasa-Lhoret Rو and Chiasson
J-L. In International Textbook of Diabetes Mellitus.
DeFronzo R.A, Ferrannini E, Zimmet P, Alberti K.G.M.M (Eds.) In: α-Glucosidase inhibitors, (2006) 322-331.
[4] Hati S, Madurkar SM, Bathula C, Thulluri C, Agarwal R, Siddiqui FA, Dangi P, Adepally U, Singh A, Singh S, Sen S. Synthesis and biological evaluation of small molecules as potent glucosidase inhibitors. Eur. J .Med. Chem. (2015) 100:188–196.
[5] Kumar S, Narwal S, Kumar V, Prakash O. α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacogn. Rev. )2011) 5(9):19-29.
[6] Yin Z, Zhang W, Feng F, Zhang Y, Kang W. (2014). α-Glucosidase inhibitors isolated from medicinal plants. Food Sc. Hum. Wellness. (2014) 3: 136-174.
[7] Khosravi A, Vaezi G, Hojati V, Abdi K. Study on the interaction of triaryl-dihydro-1,2,4-oxadiazoles with α-glucosidase. Daru. (2020) 28(1):109-117
[8] Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. (2016) 24(5):547-553.
[9] Tiwari BK, Pandey KB, Abidi AB, Rizvi SI. Markers of Oxidative Stress during Diabetes Mellitus. J. Biomark. (2013) 2013:378790.
[10] Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ. Med. J. (2012) 12(1):5-18.
[11] F. Paneni, J. A. Beckman, M. A. Creager, and F. Cosentino. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. European Heart Journal. (2013) 34(31): 2436–2443.
[12] Suresh L., Kumar P.S.V., Poornachandra Y., Kumar C.G., Chandramouli G.V.P. Design, synthesis and evaluation of novel pyrazolo-pyrimido[4,5-d]pyrimidine derivatives as potent antibacterial and biofilm inhibitors. Bioorg. Med. Chem. Lett. (2017) 27:1451–1457.
[13] Zhang J., Peng J.-F., Bai Y.-B., Wang P., Wang T., Gao J.-M., Zhang Z.-T. Synthesis of pyrazolo[1,5-a]pyrimidine derivatives and their antifungal activities against phytopathogenic fungi in vitro. Mol. Divers. (2016) 20:887–896.
[14] Mohamed M.S., Kamel R., Fatahala S.S. Synthesis and biological evaluation of some thio containing pyrrolo[2,3-d]Pyrimidine derivatives for their anti-inflammatory and anti-microbial activities. Eur. J. Med. Chem. (2010) 45:2994–3004.
[15] Alam O., Khan S.A., Siddiqui N., Ahsan W., Verma S.P., Gilani S.J. Antihypertensive activity of newer 1,4-dihydro-5-pyrimidine carboxamides: Synthesis and pharmacological evaluation. Eur. J. Med. Chem. (2010) 45:5113–5119.
[16] Hafez H.N., Hussein H.A., El-Gazzar A.-R. Synthesis of substituted thieno[2,3-d]pyrimidine-2,4-dithiones and their S-glycoside analogues as potential antiviral and antibacterial agents. Eur. J. Med. Chem. (2010) 45:4026–4034.
[17] Hese S.V., Meshram R.J., Kamble R.D., Mogle P.P., Patil K.K., Kamble S.S., Gacche R.N., Dawane B.S. Antidiabetic and allied biochemical roles of new chromeno-pyrano pyrimidine compounds: Synthesis, in vitro and in silico analysis. Med. Chem. Res. (2017) 26:805–818.
[18] Wang S.-B., Deng X.-Q., Zheng Y., Yuan Y.-P., Quan Z.-S., Guan L.-P. Synthesis and evaluation of anticonvulsant and antidepressant activities of 5-alkoxytetrazolo[1,5-c]thieno[2,3-e]pyrimidine derivatives. Eur. J. Med. Chem. (2012) 56:139–144.
[19] Ismail, Kuthati B., Thalari G., Bommarapu V., Mulakayala C., Chitta S.K., Mulakayala N. Synthesis of novel spiro pyrazolo [4,3-d] pyrimidinones and spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3′-indoline]-2′,4(3H)-diones and their evaluation for anticancer activity. Bioorg. Med. Chem. Lett. (2017) 27:1446–1450.
[20] de la Garza-Rodea AS, Knaän-Shanzer S, den Hartigh JD, Verhaegen AP, van Bekkum DW. Anomer-equilibrated streptozotocin solution for the induction of experimental diabetes in mice (Mus musculus). J. Am. Assoc. Lab. Anim. Sci. (2010) 49:40-44.
[21] OECD, 2001. OECD Guidelines for Testing of Chemicals: Acute Oral Toxicity – Acute Toxic Class Method. Test No. 423, Adopted 22nd March 1996, and Revised Method Adopted 17th December 2001, OECD, Paris.
[22] Luna LG. Manual of histological staining methods of the armed forces Institute of Pathology. New York: Blakiston Division, McGraw Hill; 1968. p. 258.
[23] Miralinaghi P., Salimi M., Amirhamzeh A., Norouzi M., Hirsa Mostafapour Kandelousi HM., Shafiee A., Amini M. Synthesis, molecular docking study, and anticancer activity of triaryl-1,2,4-oxadiazole. J Med Chem. (2013) 22:4253-4262.
- Abstract Viewed: 363 times
- IJPS_Volume 18_Issue 1_Pages 65-75 Downloaded: 297 times