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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

Author(s): Mahmoud Balbaa*, Doaa Awad, Ahmad Abd Elaal, Shimaa Mahsoub, Mayssaa Moharram, Omayma Sadek, Nadjet Rezki, Mohamed Reda Aouad, Mohamed El-Taher Ibrahim Badawy and El Sayed Helmy El Ashry

Volume 16, Issue 6, 2019

Page: [696 - 710] Pages: 15

DOI: 10.2174/1573413715666181212150955

Price: $65

Abstract

Background: 1,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope.

Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties.

Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity.

Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

Keywords: Antioxidant activity, α-Glucosidase, β -Glucuronidase, Thioglycosides, 1, 2, 4-Triazoles, Imidazoles, Molecular docking.

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[1]
Halliwell, B. Free radicals, antioxidants, and human disease: Curiosity, cause, or consequence? The Lancet, 1994, 344, 721-724.
[2]
Langseth, L. From the editor: Antioxidants and diseases of the brain. Antioxidant Vit. Newslett, 1993, 4
[3]
Kalam, S.; Gul, M.Z.; Singh, R.; Ankati, S. Free radicals: Implications in etiology of chronic diseases and their amelioration through nutraceuticals. Pharmacologia, 2015, 6, 11-20.
[4]
Lü, J-M.; Lin, P.H.; Yao, Q.; Chen, C. Chemical and molecular mechanisms of antioxidants: Experimental approaches and model systems. J. Cell. Mol. Med., 2010, 14, 840-860.
[5]
Shen, X.; Saburi, W.; Gai, Z.; Kato, K.; Ojima-Kato, T.; Yu, J.; Komoda, K.; Kido, Y.; Matsui, H.; Mori, H. Structural analysis of the α-glucosidase hag provides new insights into substrate specificity and catalytic mechanism. Acta Crystallogr. Sect D Biol. Crystallogr., 2015, 71, 1382-1391.
[6]
Jacob, R.A. The integrated antioxidant system. Nutr. Res., 1995, 15, 755-766.
[7]
Fujita, K.; Miyamura, T.; Sano, M.; Kato, I.; Takegawa, K. Transfer of high-mannose-type oligosaccharides to disaccharides by endo-β-n-acetylglucosaminidase from arthrobacter protophormiae. J. Biosci. Bioeng., 2002, 93, 614-617.
[8]
Balbaa, M.; Shibli, A.; Hosna, R.; Yusef, H.; Ahmed, T.A.B.; El Ashry, E.S.H. Biological effect of glycosyl-oxadiazolinethione and glycosyl-sulfanyloxadiazole derivatives through their in vitro inhibition of glycosidases from bacteria and normal or diabetic rats. Lett. Drug Des. Discov., 2015, 12, 211-218.
[9]
Stauffert, F.; Bodlenner, A.; Trinh, T.M.N.; García-Moreno, M.I.; Mellet, C.O.; Nierengarten, J-F.; Compain, P. Understanding multivalent effects in glycosidase inhibition using C-glycoside click clusters as molecular probes. New J. Chem., 2016, 40, 7421-7430.
[10]
Balbaa, M.; Mansour, H.; El-Sawy, H.; El-Ashry, E.S.H. Inhibition of some hepatic glycosidases by the diseco nucleoside, 4-amino-3-(d-glucopentitol-1-yl)-5-mercapto-1, 2, 4-triazole and its 3-methyl analog. Nucleosides. Nucl. Nucl. Acids, 2002, 21, 695-708.
[11]
Chiba, S. Molecular mechanism in α-glucosidase and glucoamylase. Biosci. Biotechnol. Biochem., 1997, 61, 1233-1239.
[12]
Khan, K.M.; Rahim, F.; Halim, S.A.; Taha, M.; Khan, M.; Perveen, S.; Mesaik, M.A.; Choudhary, M.I. Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking. Bioorg. Med. Chem., 2011, 19, 4286-4294.
[13]
Sperker, B.; Backman, J.T.; Kroemer, H.K. The role of β-glucuronidase in drug disposition and drug targeting in humans. Clin. Pharmacokinet., 1997, 33, 18-31.
[14]
Kim, D-H.; Jin, Y-H. Intestinal bacterial β-glucuronidase activity of patients with colon cancer. Arch. Pharm. Res., 2001, 24, 564-567.
[15]
Cheng, T.C.; Roffler, S.R.; Tzou, S.C.; Chuang, K-H.; Su, Y.C.; Chuang, C.H.; Kao, C.H.; Chen, C.S.; Harn, I.H.; Liu, K.Y. An activity-based near-infrared glucuronide trapping probe for imaging β-glucuronidase expression in deep tissues. J. Am. Chem. Soc., 2012, 134, 3103-3110.
[16]
Juan, T.Y.; Roffler, S.R.; Hou, H-S.; Huang, S-M.; Chen, K.C.; Leu, Y.L.; Prijovich, Z.M.; Yu, C.P.; Wu, C.C.; Sun, G-H. Antiangiogenesis targeting tumor microenvironment synergizes glucuronide prodrug antitumor activity. Clin. Cancer Res., 2009, 15, 4600-4611.
[17]
Baharudin, M.S.; Taha, M.; Imran, S.; Ismail, N.H.; Rahim, F.; Javid, M.T.; Khan, K.M.; Ali, M. Synthesis of indole analogs as potent β-glucuronidase inhibitors. Bioorg. Chem., 2017, 72, 323-332.
[18]
Balbaa, M.; Abdel-Hady, N.; El-Rashidy, F.; Awad, L.; El-Ashry, E-S.H.; Schmidt, R.R. Inhibition of some hepatic lysosomal glycosidases by ethanolamines and phenyl 6-deoxy-6-(morpholin-4-yl)-β-d-glucopyranoside. Carbohydr. Res., 1999, 317, 100-109.
[19]
Gong, Z.; Peng, Y.; Qiu, J.; Cao, A.; Wang, G.; Peng, Z. Synthesis, in vitro α-glucosidase inhibitory activity and molecular docking studies of novel benzothiazole-triazole derivatives. Molecules, 2017, 22, 1555-1565.
[20]
Gerber-Lemaire, S.; Juillerat-Jeanneret, L. Glycosylation pathways as drug targets for cancer: Glycosidase inhibitors. Mini Rev. Med. Chem., 2006, 6, 1043-1052.
[21]
de Melo, E.B.; da Silveira, G.A.; Carvalho, I. A-and β-glucosidase inhibitors: Chemical structure and biological activity. Tetrahedron, 2006, 62, 10277-10302.
[22]
Asano, N. Glycosidase inhibitors: Update and perspectives on practical use. Glycobiology, 2003, 13, 93R-104R.
[23]
Vocadlo, D.J.; Hang, H.C.; Kim, E-J.; Hanover, J.A.; Bertozzi, C.R. A chemical approach for identifying O-GLcNAc-modified proteins in cells. Proc. Natl. Acad. Sci., 2003, 100, 9116-9121.
[24]
Rani, M.; Sharma, S.; Chauhan, R.; Sharma, S.; Dwivedi, J. Synthesis, characterization and antibacterial evaluation of some azole derivatives. Ind. J. Pharm. Edu. Res., 2017, 51, 650-655.
[25]
Chawla, G.; Naaz, B.; Siddiqui, A.A. Exploring 1, 3, 4-oxadiazole scaffold for anti-inflammatory and analgesic activities: A review of literature from 2005-2016. Mini Rev. Med. Chem., 2018, 18, 216-233.
[26]
Güzeldemirci, N.U.; Pehlivan, E.; Naesens, L. Synthesis and antiviral activity evaluation of new 4-thiazolidinones bearing an imidazo [2, 1-b] thiazole moiety. Marmara Pharm. J., 2018, 22, 237-248.
[27]
Aouad, M.R.; Mayaba, M.M.; Naqvi, A.; Sanaa, K. Bardaweel, S.K.; Al‑blewi, F.F.; Messali, M.; Rezki, N. Design, synthesis, ex silico and in vitro antimicrobial screenings of novel 1,2,4‑triazoles carrying 1,2,3‑triazole scaffold with lipophilic side chain tether. Chem. Cent. J., 2017, 11, 117-129.
[28]
Siddiqui, S.M.; Salahuddin, A.; Azam, A. Synthesis, characterization and antiamoebic activity of some hydrazone and azole derivatives bearing pyridyl moiety as a promising heterocyclic scaffold. Eur. J. Med. Chem., 2012, 49, 411-416.
[29]
Hou, Z.; Nakanishi, I.; Kinoshita, T.; Takei, Y.; Yasue, M.; Misu, R.; Suzuki, Y.; Nakamura, S.; Kure, T.; Ohno, H. Structure-based design of novel potent protein kinase ck2 (ck2) inhibitors with phenyl-azole scaffolds. J. Med. Chem., 2012, 55, 2899-2903.
[30]
El‐Ashry, E.S.H.; El Nemr, A. Synthesis of naturally occurring nitrogen heterocycles from carbohydrates; John Wiley & Sons, 2008.
[31]
He, X-P.; Zeng, Y-L.; Zang, Y.; Li, J.; Field, R.A.; Chen, G-R. Carbohydrate CuAAC click chemistry for therapy and diagnosis. Carbohydr. Res., 2016, 429, 1-22.
[32]
El‐Ashry, E.S.H.; Rashed, N.; Awad, L.F.; Ramadan, E.S.
Abdel‐Maggeed, S.M.; Rezki, N. Synthesis of 5‐aryl‐3‐glycosylthio‐4‐phenyl‐4h‐1, 2, 4‐triazoles and their acyclic analogs under conventional and microwave conditions. J. Carbohydr. Chem., 2008, 27, 70-85.
[33]
Rezki, N.; Rashed, N.; Awad, L.; Ramadan, E.; Abdel-Maggeed, S.; El‐Ashry, E.S.H. Regio-and stereoselective synthesis of thioglycosides from 4, 5-diphenyl-and 3, 4, 5-triphenylimidazole-2-thione. Phosph. Sulfur Silicon, 2009, 184, 1759-1767.
[34]
Randhawa, M.A. Calculation of LD50 values from the method of miller and tainter, 1944. J. Ayub Med. Coll. Abbottabad, 2009, 21, 184-185.
[35]
Balbaa, M.; Omran, H.; Abdel-Monem, N.; El-Sayed, M.; Abdelmeguid, N. Antioxidants and radical scavenging role of Leek (Allium kurrat) against aflatoxin-contaminated peanut. Toxin Rev., 2017.
[http://dx.doi.org/10.1080/15569543.2017.1387152]
[36]
Salahuddin, K.; Prasad, R.; Kumar, S.; Visavadia, M.D. Isolation of soil thermophilic strains of actinomycetes for the production of α-amylase. Afr. J. Biotechnol., 2011, 10, 17831-17236.
[37]
Sutherland, M.W.; Learmonth, B.A. The tetrazolium dyes mts and xtt provide new quantitative assays for superoxide and superoxide dismutase. Free Radic. Res., 1997, 27, 283-289.
[38]
Habig, W.H.; Pabst, M.J.; Jakoby, W.B. Glutathione s-transferases the first enzymatic step in mercapturic acid formation. J. Biol. Chem., 1974, 249, 7130-7139.
[39]
Paglia, D.E.; Valentine, W.N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med., 1967, 70, 158-169.
[40]
Aebi, H. Catalase in vitro. In: Methods Enzymol., 105. Elsevier, (1984):121-126.
[41]
Tappel, A.; Zalkin, H. Lipide peroxidation in isolated mitochondria. Arch. Biochem. Biophys., 1959, 80, 326-332.
[42]
Balba, M.; El-Hady, N.A.; Taha, N.; Rezki, N.; El‐Ashry, E.S.H. Inhibition of α-glucosidase and α-amylase by diaryl derivatives of imidazole-thione and 1, 2, 4-triazole-thiol. Eur. J. Med. Chem., 2011, 46, 2596-2601.
[43]
Dowd, J.E.; Riggs, D.S. A comparison of estimates of Michaelis-Menten kinetic constants from various linear transformations. J. Biol. Chem., 1965, 240, 863-869.
[44]
Gornall, A.G.; Bardawill, C.J.; David, M.M. Determination of serum proteins by means of the biuret reaction. J. Biol. Chem., 1949, 177, 751-766.
[45]
Molecular Operating Environment (MOE), 2013.08; Chemical Computing Group ULC, 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, , 2018.
[46]
Michikawa, M.; Ichinose, H.; Momma, M.; Biely, P.; Jongkees, S.; Yoshida, M.; Kotake, T.; Tsumuraya, Y.; Withers, S.G.; Fujimoto, Z. Structural and biochemical characterization of glycoside hydrolase family 79 β-glucuronidase from acidobacterium capsulatum. J. Biol. Chem., 2012, 287, 14069-14077.
[47]
Halgren, T.A. Mmff vi. Mmff94s option for energy minimization studies. J. Comput. Chem., 1999, 20, 720-729.
[48]
Vilar, S.; Cozza, G.; Moro, S. Medicinal chemistry and the molecular operating environment (MOE): Application of QSAR and molecular docking to drug discovery. Curr. Top. Med. Chem., 2008, 8, 1555-1572.
[49]
Labute, P. Protonate 3d: Assignment of ionization states and hydrogen coordinates to macromolecular structures. Proteins: Structure, Func. Bioinf., 2009, 75, 187-205.
[50]
Goto, J.; Kataoka, R.; Muta, H.; Hirayama, N. Asedock-docking based on alpha spheres and excluded volumes. J. Chem. Inf. Model., 2008, 48, 583-590.
[51]
Hansch, C.; Fujita, T. P-σ-π analysis. A method for the correlation of biological activity and chemical structure. J. Am. Chem. Soc., 1964, 86, 1616-1626.
[52]
Dassault Systèmes, BIOVIA Discovery Studio Modeling Environment, Release 2017; San Diego: Dassault Systèmes, 2016.
[53]
De Oliveira, D.B.; Gaudio, A.C. Buildqsar: A new computer program for QSAR analysis. Quant Struct.-. Activ. Relat., 2001, 19, 599-601.
[54]
Gramatica, P. Principles of qsar models validation: Internal and external. QSAR & Combinatorial Sci, 2007, 26, 694-701.
[55]
Alexander, D.; Tropsha, A.; Winkler, D.A. Beware of r2: Simple, unambiguous assessment of the prediction accuracy of QSAR and QSPR models. J. Chem. Inf. Model., 2015, 55, 1316-1322.
[56]
Al-Ali, A.; Alkhawajah, A.A.; Randhawa, M.A.; Shaikh, N.A. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J. Ayub Med. Coll. Abbottabad, 2008, 20, 25-27.
[57]
Grodnitzky, J.A.; Coats, J.R. Qsar evaluation of monoterpenoids’ insecticidal activity. J. Agric. Food Chem., 2002, 50, 4576-4580.
[58]
Chang, H.J.; Kim, H.J.; Chun, H.S. Quantitative structure-activity relationship (QSAR) for neuroprotective activity of terpenoids. Life Sci., 2007, 80, 835-841.
[59]
Tong, F.; Coats, J.R. Quantitative structure-activity relationships of monoterpenoid binding activities to the housefly GABA receptor. Manage. Sci., 2012, 68, 1122-1129.
[60]
Kumar, P.; Narasimhan, B.; Sharma, D.; Judge, V.; Narang, R. Hansch analysis of substituted benzoic acid benzylidene/furan-2-yl-methylene hydrazides as antimicrobial agents. Eur. J. Med. Chem., 2009, 44, 1853-1863.
[61]
Takayama, C.; Fujinami, A. Quantitative structure-activity relationships of antifungal n-phenylsuccinimides and n-phenyl-1, 2-dimethylcyclopropanedicarboximides. Pestic. Biochem. Physiol., 1979, 12, 163-171.
[62]
da Rocha, D.R.; Santos, W.C.; Lima, E.S.; Ferreira, V.F. Synthesis of 1, 2, 3-triazole glycoconjugates as inhibitors of α-glucosidases. Carbohydr. Res., 2012, 350, 14-19.
[63]
Ellmers, B.R.; Rhinehart, B.L.; Robinson, K.M. Castanospermine: An apparent tight-binding inhibitor of hepatic lysosomal alpha-glucosidase. Biochem. Pharmacol., 1987, 36, 2381-2385.
[64]
Berg, J.M.; Tymoczko, J.; Gatto, J.G. Stryer: Biochemistry. WH Freeman and Company., 2002, 5, 306-307.
[65]
Hughes, A.; Rudge, A. Deoxynojirimycin: Synthesis and biological activity. Nat. Prod. Rep., 1994, 11, 135-162.
[66]
Poláková, M.; Stanton, R.; Wilson, I.B.H.; Holková, I.; Šesták, S.; Machová, E.; Jandová, Z.; Kóňa, J. Click chemistry synthesis of 1-(α-D-mannopyranosyl)-1,2,3-triazoles for inhibition of α-mannosidases. Carbohydr. Res., 2015, 406, 34-40.
[67]
Onodera, S.; Matsui, H.; Chiba, S. Single active site mechanism of rabbit liver acid α-glucosidase. The J. Biochem., 1989, 105, 611-618.
[68]
Chiba, S. A historical perspective for the catalytic reaction mechanism of glycosidase; so as to bring about breakthrough in confusing situation. Biosci. Biotechnol. Biochem., 2012, 76, 215-231.
[69]
Yoshimizu, M.; Tajima, Y.; Matsuzawa, F.; Aikawa, S.I.; Iwamoto, K.; Kobayashi, T.; Edmunds, T.; Fujishima, K.; Tsuji, D.; Itoh, K. Binding parameters and thermodynamics of the interaction of imino sugars with a recombinant human acid α-glucosidase (alglucosidase alfa): Insight into the complex formation mechanism. Clin. Chim. Acta, 2008, 391, 68-73.
[70]
Smesh, S.; Madhuri, K. Triazolyl glycoconjugates and their impact in medicinal chemistry. Org. Chem. Ind. J., 2016, 12, 104-125.
[71]
Sorrenti, V.; Salerno, L.; Di Giacomo, C.; Acquaviva, R.; Siracusa, M.; Vanella, A. Imidazole derivatives as antioxidants and selective inhibitors of nnos. Nitric Oxide, 2006, 14, 45-50.
[72]
Naik, N.; Kumar, H.V.; Rangaswamy, J.; Harini, S.T.; Umeshkumar, T.C. Three component one pot synthesis of 5-Substituted 1-Aryl-2,3-diphenyl imidazoles: A novel class of promising antioxidants. J. Appl. Pharm. Sci., 2012, 2, 67-74.
[73]
Singh, P.; Kumar, R.; Tiwari, S.; Khanna, R.S.; Tewari, A.K.; Khanna, H.D. Docking, synthesis and evaluation of antioxidant activity of 2,4,5-triaryl imidazole. Clin. Med. Biochemistry, 2015, 1, 1-4.
[74]
Charles, E.O. Molecular Polarity. In: virtual chembook, Elmhurst college, 2003.
[75]
Kuramitsu, Y.; Hamada, J.I.; Tsuruoka, T.; Morikawa, K.; Kobayashi, H.; Hosokawa, M. A new anti-metastatic drug, ND-2001, inhibits lung metastases in rat hepatoma cells by suppressing haptotaxis of tumor cells toward laminin. Anticancer Drugs, 1998, 9, 88-92.
[76]
Michiels, C.; Remacle, J. Use of the inhibition of enzymatic antioxidant systems in order to evaluate their physiological importance. FEBS J., 1988, 177, 435-441.
[77]
Ekinci, D.; Cankaya, M.; Gül, İ.; Coban, T.A. Susceptibility of cord blood antioxidant enzymes glutathione reductase, glutathione peroxidase and glutathione s-transferase to different antibiotics: In vitro approach. J. Enzyme Inhib. Med. Chem., 2013, 28, 824-829.

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