Antiglycation Activity of Triazole Schiff’s Bases Against Fructosemediated Glycation: In Vitro and In Silico Study

Author(s): Muniza Shaikh, Salman Siddiqui, Humaira Zafar, Uzma Naqeeb, Fakiha Subzwari, Rehan Imad, Khalid M. Khan, Muhammad I. Choudhary*

Journal Name: Medicinal Chemistry

Volume 16 , Issue 4 , 2020


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Abstract:

Background: Advanced glycation end products (AGEs) are known to be involved in the pathophysiology of diabetic complications, neurodegenerative diseases, and aging. Preventing the formation of AGEs can be helpful in the management of these diseases.

Objectives: Two classes of previously synthesized traizole Schiff’s bases (4H-1,2,4-triazole-4- Schiff’s bases 1-14, and 4H-1,2,4-triazole-3-Schiff’s bases 15-23) were evaluated for their in vitro antiglycation activity.

Methods: In vitro fructose-mediated human serum albumin (HSA) glycation assay was employed to assess the antiglycation activity of triazole Schiff’s bases. The active compounds were subjected to cytotoxicity analysis by MTT assay on mouse fibroblast (3T3) cell line. Molecular docking and simulation studies were carried out to evaluate the interactions and stability of compounds with HSA. Anti-hyperglycemic and antioxidant activities of selected non-cytotoxic compounds were evaluated by in vitro α-glucosidase inhibition, and DPPH free radical scavenging assays, respectively.

Results: Compound 1 (IC50=47.30±0.38 µM) from 4H-1,2,4-triazole-4-Schiff’s bases has exhibited antiglycation activity comparable to standard rutin (IC50=54.5±0.05 µM) along with a stable RMSD profile in MD simulation studies. Compound 1 also exhibited a potent α-glucosidase inhibitory activity, and moderate antioxidant property. Other derivatives showed a weak antiglycation activity with IC50 values between 248.1-637.7 µM. Compounds with potential antiglycation profile were found to be non-cytotoxic in a cellular assay.

Conclusion: The study identifies triazole Schiff’s bases active against fructose-mediated glycation of HSA, thus indicates their potential against late diabetic complications due to production of advancedend products (AGEs).

Keywords: Antiglycation activity, triazole Schiff's bases, diabetes, fructose, rutin, human serum albumin.

[1]
Vlassara, H. Recent progress in advanced glycation end products and diabetic complications. Diabetes, 1997, 46(Suppl. 2), S19-S25.
[http://dx.doi.org/10.2337/diab.46.2.S19] [PMID: 9285494]
[2]
Vlassara, H.; Palace, M.R. Glycoxidation: the menace of diabetes and aging. Mt. Sinai J. Med., 2003, 70(4), 232-241.
[PMID: 12968196]
[3]
Goldin, A.; Beckman, J.A.; Schmidt, A.M.; Creager, M.A. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation, 2006, 114(6), 597-605.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.621854] [PMID: 16894049]
[4]
Ahmed, N. Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res. Clin. Pract., 2005, 67(1), 3-21.
[http://dx.doi.org/10.1016/j.diabres.2004.09.004] [PMID: 15620429]
[5]
Stitt, A.W. The maillard reaction in eye diseases. Ann. N. Y. Acad. Sci., 2005, 1043(1), 582-597.
[http://dx.doi.org/10.1196/annals.1338.066] [PMID: 16037281]
[6]
Forbes, J.M.; Yee, L.T.; Thallas, V.; Lassila, M.; Candido, R.; Jandeleit-Dahm, K.A.; Thomas, M.C.; Burns, W.C.; Deemer, E.K.; Thorpe, S.R.; Cooper, M.E.; Allen, T.J. Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes, 2004, 53(7), 1813-1823.
[http://dx.doi.org/10.2337/diabetes.53.7.1813] [PMID: 15220206]
[7]
Yamamoto, Y.; Doi, T.; Kato, I.; Shinohara, H.; Sakurai, S.; Yonekura, H.; Watanabe, T.; Myint, K.M.; Harashima, A.; Takeuchi, M.; Takasawa, S.; Okamoto, H.; Hashimoto, N.; Asano, M.; Yamamoto, H. Receptor for advanced glycation end products is a promising target of diabetic nephropathy. Ann. N. Y. Acad. Sci., 2005, 1043(1), 562-566.
[http://dx.doi.org/10.1196/annals.1333.064] [PMID: 16037279]
[8]
Jono, T.; Kimura, T.; Takamatsu, J.; Nagai, R.; Miyazaki, K.; Yuzuriha, T.; Kitamura, T.; Horiuchi, S. Accumulation of imidazolone, pentosidine and N(epsilon)-(carboxymethyl)lysine in hippocampal CA4 pyramidal neurons of aged human brain. Pathol. Int., 2002, 52(9), 563-571.
[http://dx.doi.org/10.1046/j.1320-5463.2002.01390.x] [PMID: 12406185]
[9]
Bunn, H.F.; Higgins, P.J. Reaction of monosaccharides with proteins: possible evolutionary significance. Science, 1981, 213(4504), 222-224.
[http://dx.doi.org/10.1126/science.12192669] [PMID: 12192669]
[10]
Collino, M. High dietary fructose intake: Sweet or bitter life? World J. Diabetes, 2011, 2(6), 77-81.
[http://dx.doi.org/10.4239/wjd.v2.i6.77] [PMID: 21860690]
[11]
Kashiwagi, A.; Obata, T.; Suzaki, M.; Takagi, Y.; Kida, Y.; Ogawa, T.; Tanaka, Y.; Asahina, T.; Ikebuchi, M.; Saeki, Y.; Kikkawa, R. Increase in cardiac muscle fructose content in streptozotocin-induced diabetic rats. Metabolism, 1992, 41(10), 1041-1046.
[http://dx.doi.org/10.1016/0026-0495(92)90283-G] [PMID: 1406291]
[12]
Lal, S.; Szwergold, B.S.; Taylor, A.H.; Randall, W.C.; Kappler, F.; Brown, T.R. Production of fructose and fructose-3-phosphate in maturing rat lenses. Invest. Ophthalmol. Vis. Sci., 1995, 36(5), 969-973.
[PMID: 7706047]
[13]
Schalkwijk, C.G.; Stehouwer, C.D.; van Hinsbergh, V.W. Fructose-mediated non-enzymatic glycation: sweet coupling or bad modification. Diabetes Metab. Res. Rev., 2004, 20(5), 369-382.
[http://dx.doi.org/10.1002/dmrr.488] [PMID: 15343583]
[14]
Zhao, W.; Devamanoharan, P.S.; Varma, S.D. Fructose induced deactivation of antioxidant enzymes: preventive effect of pyruvate. Free Radic. Res., 2000, 33(1), 23-30.
[http://dx.doi.org/10.1080/10715760000300581] [PMID: 10826918]
[15]
Bousova, I.; Vukasović, D.; Juretić, D.; Palicka, V.; Drsata, J. Enzyme activity and AGE formation in a model of AST glycoxidation by D-fructose in vitro. Acta Pharm., 2005, 55(1), 107-114.
[PMID: 15907228]
[16]
Argirova, M.; Breipohl, W. Comparison between modifications of lens proteins resulted from glycation with methylglyoxal, glyoxal, ascorbic acid, and fructose. J. Biochem. Mol. Toxicol., 2002, 16(3), 140-145.
[http://dx.doi.org/10.1002/jbt.10031] [PMID: 12112714]
[17]
Luthra, M.; Balasubramanian, D. Nonenzymatic glycation alters protein structure and stability. A study of two eye lens crystallins. J. Biol. Chem., 1993, 268(24), 18119-18127.
[PMID: 8349689]
[18]
Allarakha, S.; Ahmad, P.; Ishtikhar, M.; Zaheer, M.S.; Siddiqi, S.S.; Moinuddin, ; Ali, A. Fructosylation generates neo-epitopes on human serum albumin. IUBMB Life, 2015, 67(5), 338-347.
[http://dx.doi.org/10.1002/iub.1375] [PMID: 25914162]
[19]
Suárez, G.; Rajaram, R.; Oronsky, A.L.; Gawinowicz, M.A. Nonenzymatic glycation of bovine serum albumin by fructose (fructation). Comparison with the Maillard reaction initiated by glucose. J. Biol. Chem., 1989, 264(7), 3674-3679.
[PMID: 2537288]
[20]
Dills, W.L., Jr Protein fructosylation: fructose and the Maillard reaction. Am. J. Clin. Nutr., 1993, 58(5)(Suppl.), 779S-787S.
[http://dx.doi.org/10.1093/ajcn/58.5.779S] [PMID: 8213610]
[21]
Huby, R.; Harding, J.J. Non-enzymic glycosylation (glycation) of lens proteins by galactose and protection by aspirin and reduced glutathione. Exp. Eye Res., 1988, 47(1), 53-59.
[http://dx.doi.org/10.1016/0014-4835(88)90023-1] [PMID: 3409987]
[22]
Brownlee, M.; Vlassara, H.; Kooney, A.; Ulrich, P.; Cerami, A. Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science, 1986, 232(4758), 1629-1632.
[http://dx.doi.org/10.1126/science.3487117] [PMID: 3487117]
[23]
Hipkiss, A.R.; Michaelis, J.; Syrris, P. Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent. FEBS Lett., 1995, 371(1), 81-85.
[http://dx.doi.org/10.1016/0014-5793(95)00849-5] [PMID: 7664889]
[24]
Morimitsu, Y.; Yoshida, K.; Esaki, S.; Hirota, A. Protein glycation inhibitors from thyme (Thymus vulgaris). Biosci. Biotechnol. Biochem., 1995, 59(11), 2018-2021.
[http://dx.doi.org/10.1271/bbb.59.2018] [PMID: 8541639]
[25]
Sattarahmady, N.; Khodagholi, F.; Moosavi-Movahedi, A.A.; Heli, H.; Hakimelahi, G.H. Alginate as an antiglycating agent for human serum albumin. Int. J. Biol. Macromol., 2007, 41(2), 180-184.
[http://dx.doi.org/10.1016/j.ijbiomac.2007.01.015] [PMID: 17350677]
[26]
Blakytny, R.; Harding, J.J. Prevention of cataract in diabetic rats by aspirin, paracetamol (acetaminophen) and ibuprofen. Exp. Eye Res., 1992, 54(4), 509-518.
[http://dx.doi.org/10.1016/0014-4835(92)90129-G] [PMID: 1623937]
[27]
Thornalley, P.J.; Yurek-George, A.; Argirov, O.K. Kinetics and mechanism of the reaction of aminoguanidine with the α-oxoaldehydes glyoxal, methylglyoxal, and 3-deoxyglucosone under physiological conditions. Biochem. Pharmacol., 2000, 60(1), 55-65.
[http://dx.doi.org/10.1016/S0006-2952(00)00287-2] [PMID: 10807945]
[28]
Cooper, M.E.; Thallas, V.; Forbes, J.; Scalbert, E.; Sastra, S.; Darby, I.; Soulis, T. The cross-link breaker, N-phenacylthiazolium bromide prevents vascular advanced glycation end-product accumulation. Diabetologia, 2000, 43(5), 660-664.
[http://dx.doi.org/10.1007/s001250051355] [PMID: 10855541]
[29]
Booth, A.A.; Khalifah, R.G.; Todd, P.; Hudson, B.G. In vitro kinetic studies of formation of antigenic advanced glycation end products (AGEs). Novel inhibition of post-Amadori glycation pathways. J. Biol. Chem., 1997, 272(9), 5430-5437.
[http://dx.doi.org/10.1074/jbc.272.9.5430] [PMID: 9038143]
[30]
Kim, H.Y.; Lee, J.M.; Yokozawa, T.; Sakata, K.; Lee, S. Protective activity of flavonoid and flavonoid glycosides against glucose-mediated protein damage. Food Chem., 2011, 126(3), 892-895.
[http://dx.doi.org/10.1016/j.foodchem.2010.11.068]
[31]
Whittier, F.; Spinowitz, B.; Wuerth, J.P. Pimagedine safety profile in patients with type 1 diabetes. J. Am. Soc. Nephrol., 1999, 10(9), 184A.
[32]
Jahan, H.; Choudhary, M.I. Glycation, carbonyl stress and AGEs inhibitors: a patent review. Expert Opin. Ther. Pat., 2015, 25(11), 1267-1284.
[PMID: 26293545]
[33]
Mohammed Iqbal, A.K.; Khan, A.Y.; Kalashetti, M.B.; Belavagi, N.S.; Gong, Y.D.; Khazi, I.A. Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring. Eur. J. Med. Chem., 2012, 53, 308-315.
[http://dx.doi.org/10.1016/j.ejmech.2012.04.015] [PMID: 22575535]
[34]
Fehrentz, J.A.; Bibian, M.; Moulin, A.; Martinez, J. Novel 1, 2, 4- triazole derivatives and process of manufacturing thereof., US patent 12/405,588. March 17,. 2009.
[35]
Smith, D.G.; Ward, R.W. Diamino-1, 2, 4-triazole-carboxylic and derivatives as GSK-3 inhibitors., US patent WO0109106. 2001.
[36]
Aswathanarayanappa, C.; Bheemappa, E.; Bodke, Y.D.; Biradar, S.; Sindhe, A.; Peethambar, S.K.; Ningegowda, R. Synthesis, in vitro and in vivo anti-hyperglycemic activity of 1,2,4-triazolebenzylidene and 1,3,4-thiadiazole derivatives. Synthesis, 2014, 6(4), 1245-1255.
[37]
Li, B.L.; Li, B.; Zhang, R.L.; Zhao, J.J.; Wang, X.F.; Liu, Y.M.; Shi, Y.P.; Liu, J.B.; Chen, B.Q. Synthesis and antiproliferative evaluation of novel 1,2,4-triazole derivatives incorporating benzisoselenazolone scaffold. Bioorg. Med. Chem. Lett., 2016, 26(4), 1279-1281.
[http://dx.doi.org/10.1016/j.bmcl.2016.01.017] [PMID: 26786698]
[38]
Chen, X.; Shi, Y.M.; Huang, C.; Xia, S.; Yang, L.J.; Yang, X.D. Novel dibenzo[b,d]furan-1H-1,2,4-triazole derivatives: Synthesis and antitumor activity. Anticancer. Agents Med. Chem., 2016, 16(3), 377-386.
[http://dx.doi.org/10.2174/1871520615666150817115913] [PMID: 26278547]
[39]
Maddila, S.; Momin, M.; Gorle, S.; Palakondu, L.; Jonnalagadda, S.B. Synthesis and antioxidant evaluation of novel phenothiazine linked substituted benzylideneamino-1, 2, 4-triazole derivatives. J. Chil. Chem. Soc., 2015, 60(2), 2919-2923.
[http://dx.doi.org/10.4067/S0717-97072015000200012]
[40]
Godhania, D.R.; Jogela, A.A.; Sanghanib, A.M.; Mehtaa, J.P. Synthesis and biological screening of 1, 2, 4-triazole derivatives. Indian J. Chem., 2015, 54, 556-564.
[41]
Xu, Y.Y.; Qian, A.R.; Cao, X.F.; Ling, C.Y.; Cao, Y.B.; Wang, R.L.; Li, Y.S.; Yang, Y.S. Design and synthesis of novel triazole derivatives containing γ-lactam as potential antifungal agents. Chin. Chem. Lett., 2016, 27(5), 703-706.
[http://dx.doi.org/10.1016/j.cclet.2016.01.040]
[42]
Todoulou, O.G.; Papadaki-Valiraki, A.E.; Ikeda, S.; De Clercq, E. Synthesis and antiviral activity of some new 1H-1, 2, 4-triazole derivatives. Eur. J. Med. Chem., 1994, 29(7), 611-620.
[http://dx.doi.org/10.1016/0223-5234(94)90152-X]
[43]
Ulrich, P.C.; Cerami, A.; Wagle, D.R. Inhibition of the advanced glycosylation of proteins using substituted-1, 2, 4-triazoles., US Patent 5,318,982, Jun 7, . 1994.
[44]
Khan, K.M.; Siddiqui, S.; Saleem, M.; Taha, M.; Saad, S.M.; Perveen, S.; Choudhary, M.I. Synthesis of triazole Schiff bases: novel inhibitors of nucleotide pyrophosphatase/phosphodiesterase-1. Bioorg. Med. Chem., 2014, 22(22), 6509-6514.
[http://dx.doi.org/10.1016/j.bmc.2014.08.032] [PMID: 25440732]
[45]
Rahbar, S.; Figarola, J.L. Novel inhibitors of advanced glycation endproducts. Arch. Biochem. Biophys., 2003, 419(1), 63-79.
[http://dx.doi.org/10.1016/j.abb.2003.08.009] [PMID: 14568010]
[46]
Scudiero, D.A.; Shoemaker, R.H.; Paull, K.D.; Monks, A.; Tierney, S.; Nofziger, T.H.; Currens, M.J.; Seniff, D.; Boyd, M.R. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res., 1988, 48(17), 4827-4833.
[PMID: 3409223]
[47]
LigPrep, version 3.6; Schrödinger, LLC: New York, NY, 2015.
[48]
Wizard, P.P. 2015-4; Epik version 2.4; Schrödinger, LLC: New York, NY, 2015.
[49]
Sastry, G.M.; Adzhigirey, M.; Day, T.; Annabhimoju, R.; Sherman, W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des., 2013, 27(3), 221-234.
[http://dx.doi.org/10.1007/s10822-013-9644-8] [PMID: 23579614]
[50]
Glide, version 6.9; Schrödinger, LLC: New York, NY, 2015.
[51]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K.; Shaw, D.E.; Francis, P.; Shenkin, P.S. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem., 2004, 47(7), 1739-1749.
[http://dx.doi.org/10.1021/jm0306430] [PMID: 15027865]
[52]
Halgren, T.A.; Murphy, R.B.; Friesner, R.A.; Beard, H.S.; Frye, L.L.; Pollard, W.T.; Banks, J.L. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem., 2004, 47(7), 1750-1759.
[http://dx.doi.org/10.1021/jm030644s] [PMID: 15027866]
[53]
Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem., 2006, 49(21), 6177-6196.
[http://dx.doi.org/10.1021/jm051256o] [PMID: 17034125]
[54]
Desmond Molecular Dynamics System. D. E. Shaw Research, New York, NY, 2015. Maestro-Desmond Interoperability Tools; Schrödinger, New York, NY, 2015.
[55]
Siddiqui, M.A.; Rasheed, S.; Saquib, Q.; Al-Khedhairy, A.A.; Al-Said, M.S.; Musarrat, J.; Choudhary, M.I. In-Vitro dual inhibition of protein glycation, and oxidation by some Arabian plants. BMC Complement. Altern. Med., 2016, 16(1), 276.
[http://dx.doi.org/10.1186/s12906-016-1225-7] [PMID: 27495289]
[56]
Matsui, T.; Yoshimoto, C.; Osajima, K.; Oki, T.; Osajima, Y. In vitro survey of α-glucosidase inhibitory food components. Biosci. Biotechnol. Biochem., 1996, 60(12), 2019-2022.
[http://dx.doi.org/10.1271/bbb.60.2019] [PMID: 8988634]
[57]
Anguizola, J.; Matsuda, R.; Barnaby, O.S.; Hoy, K.S.; Wa, C.; DeBolt, E.; Koke, M.; Hage, D.S. Review: Glycation of human serum albumin. Clin. Chim. Acta, 2013, 425, 64-76.
[http://dx.doi.org/10.1016/j.cca.2013.07.013] [PMID: 23891854]
[58]
Wang, Y.; Yu, H.; Shi, X.; Luo, Z.; Lin, D.; Huang, M. Structural mechanism of ring-opening reaction of glucose by human serum albumin. J. Biol. Chem., 2013, 288(22), 15980-15987.
[http://dx.doi.org/10.1074/jbc.M113.467027] [PMID: 23592780]
[59]
Pastukhov, A.V.; Levchenko, L.A.; Sadkov, A.P. Spectroscopic study on binding of rutin to human serum albumin. J. Mol. Struct., 2007, 842(1), 60-66.
[http://dx.doi.org/10.1016/j.molstruc.2006.12.008]


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VOLUME: 16
ISSUE: 4
Year: 2020
Published on: 21 May, 2020
Page: [575 - 591]
Pages: 17
DOI: 10.2174/1573406415666190212105718
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