Study of antidiabetic activity of two novel Schiff base derived dibromo and dichloro substituted compounds in streptozotocin-nicotinamide-induced diabetic rats: pilot study
DOI:
https://doi.org/10.1590/s2175-97902023e21159Keywords:
CNCP, CNBP, Schiff base, Dichloride substitution, Dibromid substitution, Anti-diabetic effectAnti-diabetic effectAbstract
Schiff bases are aldehyde-or ketone-like chemical compounds in which an imine or azomethine group replaces the carbonyl group. Such compounds show various beneficial biological activities, such as anti-inflammation and antioxidants. The present study addresses comprehensiveevaluation of antidiabetic effect of two novel dibromides and dichlorides substituted Schiff bases substituted Schiff bases (2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)]bis[4-chlorophenol] (CNCP) and 2, 2'-[1,2-cyclohexanediylbis(nitriloethylidyne)]bis[4-bromophenol] (CNBP) with two different doses, high (LD) and low (LD) in streptozotocin and nicotinamide induced diabetic rats. The rats were separated into normal, untreated, treated and reference groups. Except for the normal group, diabetes traits were induced in the rest animals. Insulin level was measured, and the effect of the compounds on biochemical parameters of liver function and lipid profile were evaluated. High glucose and decreased insulin level are observed in the groups. The histological evaluation confirms that the hepatic architecture in the treated animals with a low dose of CNCP is quite similar to that of the normal hepatic structure and characterized by normal central vein, hepatocytes without any fatty alterations and mild red blood cell infiltration. CNCP (LD) and CNBP (HD) are more successful in enhancing cell survival in the diabetic rat’s liver and can be responsible for causing much healthier structure and notable morphology improvement.
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Afzal HR, Khan NUH, Sultana K, Mobashar A, Lareb A, Khan A, et al. Schiff bases of pioglitazone provide better antidiabetic and potent antioxidant effect in a streptozotocin nicotinamide-induced diabetic rodent model. ACS Omega. 2021;6(6):4470-4479.
Al-Qadsy I, Saeed WS, Al-Odayni AB, Ahmed Saleh Al-Faqeeh L, Alghamdi AA, Farooqui M. Novel metformin-based schiff bases: synthesis, characterization, and antibacterial evaluation. Materials. 2020;13(3):514.
Anitha C, Sheela C, Tharmaraj P, Shanmugakala R. Studies on synthesis and spectral characterization of some transition metal complexes of azo-azomethine derivative of diaminomaleonitrile. Int J Inorg Chem. 2013(2013):Article ID 436275.
Asadi-Samani M, Kafash-Farkhad N, Azimi N, Fasihi A, Alinia-Ahandani E, Rafieian-Kopaei M. Medicinal plants with hepatoprotective activity in Iranian folk medicine. Asian Pac J Trop Biomed. 2015;5(2):146-157.
Balakumar P, Arora MK, Ganti SS, Reddy J, Singh M. Recent advances in pharmacotherapy for diabetic nephropathy: current perspectives and future directions. Pharmacol Res. 2009;60(1):24-32.
Bedia KK, Elçin O, Seda U, Fatma K, Nathaly S, Sevim R, et al. Synthesis and characterization of novel hydrazide- hydrazones and the study of their structure antituberculosis activity. Eur J Med Chem. 2006;41(11):1253-1261.
El-Hashash MA, Kadhim MA, Rizk SA. Facile synthesis, characterization of novel schiff bases and N-nucleosides bearing quinazoline moiety and evaluation of their antimicrobial effects. J Appl Chem. 2015;4:1716-1724.
Gupta SK. Topical delivery system for antiaging and skin whitening agents. Google Patents. 2010.
Kakkar R, Kalra J, Mantha SV, Prasad K. Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol Cell Biochem. 1995;151(2):113-119.
Ke YD, Delerue F, Gladbach A, Götz J, Ittner LM. Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of alzheimer’s disease. Plos One. 2009;4:E7917.
Kim SJ. Herbal Chrysanthemi Flos, oxidative damage and protection against diabetic complications. Diabetes: Oxidative Stress and Dietary Antioxidants. Elsevier. 2014.
Küçükgüzel ŞG, Küçükgüzel İ, Oral B, Sezen S, Rollas S. Detection of nimesulide metabolites in rat plasma and hepatic subcellular fractions by Hplc-Uv/Dad and Lc-Ms/ Ms studies. Eur J Drug Metab Pharmacokinet. 2005;30(1-2):127-134.
Kumar M, Padmini T, Ponnuvel K. Synthesis, characterization and antioxidant activities of schiff bases are of cholesterol. J Saudi Chem Soc. 2017;21:S322-S328.
Kumskova EM, Antonova OA, Balashov SA, Tikhaze AK, Melkumyants AM, Lankin VZ. Malonyldialdehyde and glyoxal act differently on low-density lipoproteins and endotheliocytes. Mol Cell Biochem . 2014;396(1-2):79-85.
Lenzen S. Chemistry and biology of reactive species with special reference to the antioxidative defence status in pancreatic Β-cells. Biochim Biophys Acta Gen Subj. 2017;1861(8):1929-1942.
Lin X, Liu M. Bromophenols from marine algae with potential anti-diabetic activities. J Ocean Univ China. 2017;11:533-538.
Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev. 2010;4(8):118-126.
Mabuza LP, Gamede MW, Maikoo S, Booysen IN, Ngubane PS, Khathi A. Cardioprotective effects of a ruthenium (II) schiff base complex in diet-induced prediabetic rats. Diabetes Metab Syndr Obes. 2019;12:217-223.
Mahmoud M, Zaitone S, Ammar A, Sallam S. Synthesis, structure and antidiabetic activity of chromium (III) complexes of metformin schiff bases. J Mol Struct. 2016;1108:60-70.
Matsubara T, Abe H, Arai H, Nagai K, Mima A, Kanamori H, et al. Expression of smad1 is directly associated with mesangial matrix expansion in rat diabetic nephropathy. Lab Invest. 2006;86(4):357-368.
Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, Novelli M, Ribes G. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes. 1998;47:224-229.
Ndagi U, Mhlongo N, Soliman ME. Metal complexes in cancer therapy-an update from drug design perspective. Drug Des Devel Ther. 2017;11:599-616.
Niizato T, Shiotani M, Shoji Y. Composition for treatment of diabetes and treatment of diabetes. Google Patents. 2002.
Noshahr ZS, Salmani H, Khajavi Rad A, Sahebkar A. Animal models of diabetes associated renal injury. J Diabetes Res. 2020: 9416419.
Roat R, Rao V, Doliba NM, Matschinsky FM, Tobias JW, Garcia E, et al. Alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese C57bl/6j mice. Plos One . 2014;9:E86815.
Rollas S, Gulerman N, Erdeniz H. Synthesis and antimicrobial activity of some new hydrazones of 4-fluorobenzoic acid hydrazide and 3-Acetyl-2, 5-Disubstituted-1, 3, 4-Oxadiazolines. Farmaco. 2002;57(2):171-174.
Sahiba N, Sethiya A, Soni J, Agarwal DK, Agarwal S. Saturated five-membered thiazolidines and their derivatives: from synthesis to biological applications. Top Curr Chem. 2020;378(2):1-90.
Saremi K, Rad SK, Khalilzadeh M, Hussaini J, Majid NA. In vivo acute toxicity and anti-gastric evaluation of a novel dichloro schiff base: Bax and Hsp70 alteration. Acta Biochim Biophys Sin (Shanghai). 2020;52(1):26-37.
Saremi K, Rad SK, Tayeby F, Abdulla MA, Karimian H, Majid NA. Gastroprotective activity of a novel schiff base derived dibromo substituted compound against ethanol-induced acute gastric lesions in rats. BMC Pharmacol Toxicol. 2019;20(1):13.
Schuit FC, Huypens P, Heimberg H, Pipeleers DG. Glucose sensing in pancreatic Β-cells: A model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus. Diabetes. 2001;50(1):1-11.
Shima K, Zhu M, Kuwajima M. A role of nicotinamide-induced increase in pancreatic Β-cell mass on blood glucose control after discontinuation of the treatment in partially pancreatectomized oletf rats. J Diabetes Res . 1998;41(1):1-8.
Shukla SN, Gaur P, Jhariya S, Chaurasia B, Vaidya P, Azam M. Biochemical relevance of Cr (Iii) complexes of isoniazid: synthesis, characterization, Dft, antibacterial screening, antioxidant activity and glucose-lowering effect in stz-induced diabetic rats. J Coord Chem. 2019;72(4):664-689.
Sirajuddin M, Ali S, Haider A, Shah NA, Shah A, Khan MR. Synthesis, characterization, biological screenings and interaction with calf thymus Dna as well as electrochemical studies of adducts formed by azomethine [2-((3, 5-Dimethylphenylimino) Methyl) Phenol] and organotin (Iv) chlorides. Polyhedron. 2012;40(1):19-31.
Sykuła А, Cheshchevik VT, Cheshchevik NG, Dzeikala А, Łodyga-Chruścińska E. In vitrostudy of hesperetin schiff bases antioxidant activity on rat liver mitochondria. Biotechnol Food Sci. 2018;82(2):151-159.
Thomas HE, Kay TW. Beta cell destruction in the development of autoimmune diabetes in the Non‐Obese Diabetic (Nod) mouse. Diabetes Metab J. 2000;16(4):251-261.
Torabi S, Mohammadi M, Shirvani M. Antidiabetic, antioxidant, antibacterial, and antifungal activities of vanadyl schiff base complexes. Trends Pharmacol Sci. 2018;4:87-94.
Vančo J, Marek J, Trávníček Z, Račanská E, Muselík J, Švajlenová OG. Synthesis, structural characterization, antiradical and antidiabetic activities of copper (Ii) and zinc (Ii) schiff base complexes derived from salicylaldehyde and Β-alanine. J Inorg Biochem. 2008;102(4):595-605.
Yaul A, Pethe G, Deshmukh R, Aswar A. Vanadium complexes with quadridentate schiff bases. J Therm Anal Calorim. 2013;113:745-752.
Zhao X, Wu H, Guo B, Dong R, Qiu Y, Ma PX. Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing. Biomaterials. 2017;122:34-47.
Zhou JY, Zhou SW, Zhang KB, Tang JL, Guang LX, Ying Y, et al. Chronic effects of berberine on blood, liver glucolipid metabolism and liver ppars expression in diabetic hyperlipidemic rats. Biol Pharm Bull. 2008;31(6):1169-1176.
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