1- Pharmacy Student, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 2- Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 3- Department of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 4- Department of Organic Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran , l.youseftabar@iautmu.ac.ir
Abstract: (1919 Views)
Background: Diabetes is a metabolic disease that disrupts metabolism of sugars and fats in the body. The aim of present study was to investigate the effect of isatin-schiff base derivatives on blood glucose and lipid levels in streptozotocin-induced type II diabetic rats. Materials and methods: Drugs (insulin, glibenclamide, Schiff base I and Schiff base II) were injected intraperitoneally for 14 days. After 14 days, blood samples were taken from all groups and blood glucose and lipid profiles were measured. Results: Streptozotocin injection significantly increased blood sugar, triglyceride, cholesterol and LDL, but significantly decreased blood HDL compared to the control group. Also, injection of insulin, glibenclamide, Schiff base I and different doses of Schiff base II (for 14 days) in the diabetic group significantly reduced blood sugar, triglycerides, cholesterol and LDL, but significantly increased blood HDL compared to the sham diabetic group. Injection of the lowest dose of Schiff base II (25 mg/kg) with glibenclamide (5 mg/kg) significantly reduced blood sugar compared to the control or glibenclamide group, but had no significant effect on triglyceride, cholesterol, HDL and LDL compared to the control, insulin or glibenclamide groups. Conclusion: These results indicate that the derivatives of E)) - 3- (H1-imidazole-4-yl) -2 - ((2-oxindolin-3-ylidine) amino) propanoic acid may be effective in the treatment of diabetes. The effect of Schiff base I and Schiff base II are probably due to the presence of isatin or imidazole ring and their antioxidant properties.
1. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001;414: 782-7. [DOI:10.1038/414782a]
2. Guariguata L. By the numbers: new estimates from the IDF Diabetes Atlas Update for 2012. Diabetes Res Clin Pract 2012; 98:524-5. [DOI:10.1016/j.diabres.2012.11.006]
3. Meetoo D, McGovern P, Safadi R. An epidemiological overview of diabetes across the world. Br J Nurs 2007; 16:1002-7. [DOI:10.12968/bjon.2007.16.16.27079]
4. Stenman S, Groop PH, Saloranta C, Tötterman KJ, Fyhrqvist F, Groop L. Effects of the combination of insulin and glibenclamide in Type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral hypoglycaemic agents. Diabetologia 1988; 31:206-13. [DOI:10.1007/BF00290586]
5. Minami M, Hamaue N, Endo T, Hirafuji M, Terado M, Ide H, et al. Effects of isatin, an endogenous MAO inhibitor, on dopamine (DA) and acetylcholine (ACh) concentrations in rats. Nippon Yakurigaku Zasshi Japonica 1999; 114:186-91. [DOI:10.1254/fpj.114.supplement_186]
6. Guo H. Isatin derivatives and their anti-bacterial activities. Eur J Med Chem 2019; 164:678-88. [DOI:10.1016/j.ejmech.2018.12.017]
7. Sharma PK, Balwani S, Mathur D, Malhotra S, Singh BK, Prasad AK, et al. Synthesis and anti-inflammatory activity evaluation of novel triazolyl-isatin hybrids. J Enzyme Inhib Med Chem 2016; 31:1520-6 [DOI:10.3109/14756366.2016.1151015]
8. Dar OA, Lone SA, Malik MA, Aqlan FM, Wani MY, Hashmi AA, et al. Synthesis and synergistic studies of isatin based mixed ligand complexes as potential antifungal therapeutic agents. Heliyon 2019;5: e02055. [DOI:10.1016/j.heliyon.2019.e02055]
9. Soni J, Sethiya A, Sahiba N, Agarwal DK, Agarwal S. Contemporary Progress in the Synthetic Strategies of Imidazole and its Biological Activities. Curr Org Synth 2019; 16:1078-104. [DOI:10.2174/1570179416666191007092548]
10. Bettencourt AP, Castro M, Silva JP, Fernandes F, Coutinho OP, Sousa MJ, et al. Phenolic Imidazole Derivatives with Dual Antioxidant/Antifungal Activity: Synthesis and Structure-Activity Relationship. Med Chem 2019; 15:341-51. [DOI:10.2174/1573406414666181005143431]
11. Zhan P, Liu X, Zhu J, Fang Z, Li Z, Pannecouque C, et al. Synthesis and biological evaluation of imidazole thioacetanilides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors. Bioorg Med Chem 2009; 17:5775-81. [DOI:10.1016/j.bmc.2009.07.028]
12. Hameed A, Al-Rashida M, Uroos M, Abid Ali S, Khan KM. Schiff bases in medicinal chemistry: a patent review (2010-2015). Expert opinion on therapeutic patents (EOTPEG) 2017; 27:63-79. [DOI:10.1080/13543776.2017.1252752]
13. Viegas-Junior C, Danuello A, da Silva Bolzani V, Barreiro EJ, Fraga CA. Molecular hybridization: a useful tool in the design of new drug prototypes. Curr Med Chem 2007; 14:1829-52. [DOI:10.2174/092986707781058805]
14. Shaveta, Mishra S, Singh P. Hybrid molecules: The privileged scaffolds for various pharmaceuticals. Eur J Med Chem 2016; 124:500-36. [DOI:10.1016/j.ejmech.2016.08.039]
15. Burcelin R, Eddouks M, Maury J, Kande J, Assan R, Girard J. Excessive glucose production, rather than insulin resistance, accounts for hyperglycaemia in recent-onset streptozotocin-diabetic rats. Diabetologia 1995; 38:283-90 [DOI:10.1007/BF00400632]
16. Kusunoki J, Aragane K, Kitamine T, Kozono H, Kano K, Fujinami K, et al. Postprandial hyperlipidemia in streptozotocin-induced diabetic rats is due to abnormal increase in intestinal acyl coenzyme A: cholesterol acyltransferase activity. Arterioscler Thromb Vasc Biol 2000; 20:171-8. [DOI:10.1161/01.ATV.20.1.171]
17. Abadi AH, Abou-Seri SM, Abdel-Rahman DE, Klein C, Lozach O, Meijer L. Synthesis of 3-substituted-2-oxoindole analogues and their evaluation as kinase inhibitors, anticancer and antiangiogenic agents. Eur J Med Chem 2006; 41:296-305. [DOI:10.1016/j.ejmech.2005.12.004]
18. Singh BK, Rajour HK, Prakash A. Synthesis, characterization and biological activity of transition metal complexes with Schiff bases derived from 2-nitrobenzaldehyde with glycine and methionine. Spectrochim Acta A Mol Biomol Spectrosc 2012; 143 :51-94. [DOI:10.1016/j.saa.2012.03.077]
19. Eidi A, Eidi M, Esmaeili E. Antidiabetic effect of garlic (Allium sativum L.) in normal and streptozotocin-induced diabetic rats. Phytomedicine: Int J Phytother Phytopharmacol 2006; 13:624-9. [DOI:10.1016/j.phymed.2005.09.010]
20. Aftab MF, Afridi SK, Ghaffar S, Murtaza M, Khan M, Karim A, et al. A bis-Schiff base of isatin improves methylglyoxal mediated insulin resistance in skeletal muscle cells. Arch Pharmacal Res 2015. [DOI:10.1007/s12272-015-0670-z]
21. Khan KM, Khan M, Ali M, Taha M, Rasheed S, Perveen S, et al. Synthesis of bis-Schiff bases of isatins and their antiglycation activity. Bioorg Med Chem 2009; 17:7795-801. [DOI:10.1016/j.bmc.2009.09.028]
22. Chen G, Wang Y, Hao X, Mu S, Sun Q. Simple isatin derivatives as free radical scavengers: Synthesis, biological evaluation and structure-activity relationship. Chem Cent J 2011; 5:37. [DOI:10.1186/1752-153X-5-37]
23. Afridi SK, Aftab MF, Murtaza M, Ghaffar S, Karim A, Mughal UR, et al. A new glycotoxins inhibitor attenuates insulin resistance in liver and fat cells. Biochem Biophys Res Commun 2016; 476:188-95. [DOI:10.1016/j.bbrc.2016.05.085]
24. Stetinova V, Smetanova L, Grossmann V, Anzenbacher P. In vitro and in vivo assessment of the antioxidant activity of melatonin and related indole derivatives. Gen Physiol Biophys 2002; 21:153-62.
25. Herraiz T, Galisteo J. Endogenous and dietary indoles: a class of antioxidants and radical scavengers in the ABTS assay. Free Radic Res 2004; 38:323-31. [DOI:10.1080/10611860310001648167]
26. Sabu MC, Kuttan R. Anti-diabetic activity of medicinal plants and its relationship with their antioxidant property. J. Ethnopharmacol 2002; 81:155-60. [DOI:10.1016/S0378-8741(02)00034-X]
27. Sonmez F, Gunesli Z, Kurt BZ, Gazioglu I, Avci D, Kucukislamoglu M. Synthesis, antioxidant activity and SAR study of novel spiro-isatin-based Schiff bases. Mol Divers 2019; 23:829-44. [DOI:10.1007/s11030-018-09910-7]
28. Abu-Dief AM, Abdel-Rahman LH, Abdelhamid AA, Marzouk AA, Shehata MR, Bakheet MA, et al. Synthesis and characterization of new Cr (III), Fe (III) and Cu (II) complexes incorporating multi-substituted aryl imidazole ligand: Structural, DFT, DNA binding, and biological implications. Spectrochim Acta A Mol Biomol 2020; 228:117700. [DOI:10.1016/j.saa.2019.117700]
Goleij M, Khakpai F, Montazeri M, Youseftabar-Miri L. Modulation of blood sugar level and lipid profiles by schiff base of (E)-3-(1H-imidazol-4-yl)-2-((2-oxoindolin-3-ylidene) amino) propanoicacid derivatives in streptozotocin-induced type II diabetic rats. MEDICAL SCIENCES 2021; 31 (3) :319-327 URL: http://tmuj.iautmu.ac.ir/article-1-1785-en.html