Abstract
Background & Objective: The target tetrazole glycosides were synthesized by construction of ring system by cycloaddition reaction of benzothiazole-linked nitrile derivative and sodium azide followed by N-glycosylation process and deprotection.
Methods: The triazole glycosides were prepared by applying click approach involving dipolar cycloaddition of benzothiazole possessing alkyne functionality and different glycosyl azides. The products incorporating acyclic analogs of sugar moieties were synthesized through alkylation using acyclic oxygenated halides.
Results: The anticancer activity was studied against human breast adenocarcinoma cells (MCF-7) and human normal Retina pigmented epithelium cells (RPE-1). High activities were revealed by three compounds with IC50 values 11.9-16.5 µM compared to doxorubicin (18.6 µM) in addition to other four derivatives with good inhibition activities.
Conclusion: Enzyme docking investigation was performed into cyclin-dependent kinase 2 (CDK2); a potential target for cancer medication. Compounds which have possessed highest activities revealed good fitting inside the binding site of the protein molecular surface and showed minimum binding energy.
Keywords: Thiazole, tetrazoles, 1, 2, 3-triazoles, glycosides, CDK-2, docking, breast cancer.
Graphical Abstract
[1]
Porter, P. “Westernizing” women’s risks? Breast cancer in lower-income countries. New England Journal of Medicine., 2008, 358(3), 213-216.
[3]
Lee, M.G.; Nurse, P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature, 1987, 327(6117), 31-35.
[4]
Peyressatre, M.; Prével, C.; Pellerano, M.; Morris, M.C. Targeting cyclin-dependent kinases in human cancers: From small molecules to peptide inhibitors. Cancer, 2015, 7, 179-237.
[5]
Weroha, S.J.; Lingle, W.L.; Hong, Y.; Li, S.A.; Li, J.J. Specific overexpression of cyclin E·CDK2 in early pre-invasive and primary breast tumors in female ACI rats induced by estrogen. Horm. Cancer, 2010, 1, 34-43.
[6]
Rossi, A.G.; Sawatzky, D.A.; Walker, A.; Ward, C.; Sheldrake, T.A.; Riley, N.A.; Caldicott, A.; Martinez-Losa, M.; Walker, T.R.; Duffin, R.; Gray, M.; Crescenzi, E.; Martin, M.C.; Brady, H.J.; Savill, J.S.; Dransfield, I.; Haslett, C. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat. Med., 2006, 12(9), 1056-1064.
[7]
Senderowicz, A.M. Flavopiridol the first cyclin-dependent kinase inhibitor in human clinical trials. Invest. New Drugs, 1999, 17(3), 313-320.
[8]
Dholakia, S.P.; Patel, S.A. Review: Novel heterocycles and targets for cancer therapy. Am. J. Pharm. Tech. Res., 2012, 2(2), 204-226.
[9]
Lesyk, R.; Vladzimirska, O.; Holota, S.; Zaprutko, L.; Gzella, A. New 5-substituted thiazolo[3,2-b][1,2,4]triazol-6-ones: Synthesis and anticancer evaluation. Eur. J. Med. Chem., 2007, 42(5), 641-648.
[10]
Havrylyuk, D.; Zimenkovsky, B.; Vasylenko, O.; Zaprutko, L.; Gzella, A.; Lesyk, R. Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity. Eur. J. Med. Chem., 2009, 44(4), 1396-1404.
[11]
Kaminskyy, D.; Zimenkovsky, B.; Lesyk, R. Synthesis and in vitro anticancer activity of 2,4-azolidinedione-acetic acids derivatives. Eur. J. Med. Chem., 2009, 44(9), 3627-3636.
[12]
Merino, P.; Tejero, T.; Unzurrunzaga, F.J.; Franco, S.; Chiacchio, U.; Saita, M.G.; Iannazzo, D.; Piperno, A.; Romeo, G. An efficient approach to enantiomeric isoxazolidinyl analogues of tiazofurin based on nitrone cycloaddition. Tetrahedron Asymmetry, 2005, 16(23), 3865-3876.
[13]
Franchetti, P.; Grifantini, M. Nucleoside and non-nucleoside IMP dehydrogenase inhibitors as antitumor and antiviral agents. Curr. Med. Chem., 1999, 6(7), 599-614.
[14]
Popsavin, M.; Torović, L.; Svircev, M.; Kojić, V.; Bogdanović, G.; Popsavin, V. Synthesis and antiproliferative activity of two new tiazofurin analogues with 2′-amido functionalities. Bioorg. Med. Chem. Lett., 2006, 16(10), 2773-2776.
[15]
Samrat, D.; Shyam, J.G.; Asish, K.S. Silver trifluoromethanesulfonate and metallic copper mediated syntheses of 1,2,3-triazole-O- and triazolyl glycoconjugates: Consecutive glycosylation and cyclization under one-pot condition. Tetrahedron Lett., 2016, 57(29), 3086-3090.
[16]
dos Anjos, J.V.; Filho, R.A.W.N.; do Nascimento, S.C.; Srivastava, R.M.; de Melo, S.J.; Sinou, D. Synthesis and cytotoxic profile of glycosyl–triazole linked to 1,2,4-oxadiazole moiety at C-5 through a straight-chain carbon and oxygen atoms. Eur. J. Med. Chem., 2009, 44(9), 3571-3576.
[17]
Rossi, L.L.; Basu, A. Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles. Bioorg. Med. Chem. Lett., 2005, 15(15), 3596-3599.
[18]
Carvalho, I.; Andrade, P.; Campo, V.L.; Guedes, P.M.; Sesti-Costa, R.; Silva, J.S.; Schenkman, S.; Dedola, S.; Hill, L.; Rejzek, M.; Nepogodiev, S.A.; Field, R.A. ‘Click chemistry’ synthesis of a library of 1,2,3-triazole-substituted galactose derivatives and their evaluation against trypanosoma cruziand its cell surface trans-sialidase. Bioorg. Med. Chem., 2010, 18(7), 2412-2427.
[19]
Olomola, T.O.; Klein, R.; Lobb, K.A.; Sayed, Y.; Kaye, P.T. Towards the synthesis of coumarin derivatives as potential dual-action HIV-1 protease and reverse transcriptase inhibitors. Tetrahedron Lett., 2010, 51(48), 6325-6328.
[20]
da Silva, F.D.; de Souza, M.C.B.V.; Frugulhetti, I.I.P.; Castro, H.C.; Souza, S.L.D.; de Souza, T.M.L.; Rodrigues, D.Q.; Souza, A.M.T.; Abreu, P.A.; Passamani, F.; Rodrigues, C.R.; Ferreira, V.F. Synthesis, HIV-RT inhibitory activity and SAR of 1-benzyl-1H-1,2,3-triazole derivatives of carbohydrate. Eur. J. Med. Chem., 2009, 44(1), 373-383.
[21]
Mohite, P.B.; Bhaskar, V.H. Potential pharmacological activities of tetrazoles in the new millennium. Int. J. Pharm. Tech. Res., 2011, 3(3), 1557-1566.
[22]
Osheroff, N.; Zechiedrich, E.L.; Gale, K.C. Catalytic function of DNA topoisomerase II. BioEssays, 1991, 13(6), 269-275.
[23]
Issell, B.F. The podophyllotoxin derivatives VP16-213 and VM26. Cancer Chemother. Pharmacol., 1982, 7(2-3), 73-80.
[24]
Beers, S.A.; Imakura, Y.; Dai, H.J.; Li, D.H.; Cheng, Y.C.; Lee, K.H. Antitumor agents, 99. synthetic ring C aromatized podophyllotoxin analogues as potential inhibitors of human DNA topoisomerase II. J. Nat. Prod., 1988, 51(5), 901-905.
[25]
Day, S.H.; Lin, Y.C.; Tsai, M.L. Potent cytotoxic lignans from justicia procumbens and their effects on nitric oxide and tumor necrosis factor-α production in mouse macrophages. J. Nat. Prod., 2002, 65(3), 379-381.
[26]
Kumar, C.N.S.S.P.; Parida, D.K.; Santhoshi, A.; Kota, A.K.; Sridhar, B.; Rao, V.J. Synthesis and biological evaluation of tetrazole containing compounds as possible anticancer agents. MedChemComm, 2011, 2, 486-492.
[27]
Sammelson, R.E.; Miller, R.B.; Kurth, M.J. Linear tetraheterocycles composed of both bidentate diisoxazole and bidentate isoxazole-furyl/theinyl/pyridyl motifs. J. Org. Chem., 2000, 65(7), 2225-2228.
[28]
Ryng, S.; Glowiak, T. The isoxazole heterocyclic system: Synthesis of a new model structure in immunosuppressing agents. J. Chem. Crystallogr., 1998, 28(5), 373-378.
[29]
Herr, R.J. 5-substituted-1H-tetrazoles as carboxylic acid isosteres: Medicinal chemistry and synthetic methods. Bioorg. Med. Chem., 2002, 10(11), 3379-3392.
[30]
Master, H.E.; Khan, S.I.; Poojari, K.A. Design and synthesis of low molecular weight compounds with complement inhibition activity. Bioorg. Med. Chem., 2005, 13, 4891-4899.
[31]
El-Sayed, W.A.; Abdel Megeid, R.E.; Abbas, H.S. Synthesis and Antimicrobial Activity of New 1-[(tetrazol-5-yl)methyl]indole Derivatives, their 1,2,4-Triazole Thioglycosides and Acyclic Analogs. Arch. Pharm. Res., 2011, 34(7), 1085-1096.
[32]
Jordheim, L.P.; Durantel, D.; Zoulim, F.; Dumontet, C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat. Rev. Drug Discov., 2013, 12, 447-464.
[33]
Gomha, S.M.; Ahmed, S.A.; Abdelhamid, A.O. Synthesis and cytotoxicity evaluation of some novel thiazoles, thiadiazoles, and Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones incorporating triazole moiety. Molecules, 2015, 20, 1357-1376.
[34]
Dutta, S.; Ji Gupta, S.; Kumar Sen, A. Silver trifluoromethanesulfonate and metallic copper mediated syntheses of 1,2,3-triazole-O- and triazolyl glycoconjugates: consecutive glycosylation and cyclization under one-pot condition. Tetrahedron Lett., 2016, 57, 3086-3090.
[35]
dos Anjos, J.V.; Filho, R.A.W.N.; do Nascimento, S.C.; Srivastava, R.M.; de Melo, S.J.; Sinou, D. Synthesis and cytotoxic profile of glycosyl–triazole linked to 1,2,4-oxadiazole moiety at C-5 through a straight-chain carbon and oxygen atoms. Eur. J. Med. Chem., 2009, 44, 3571-3576.
[36]
El-Sayed, W.A.; El-Kosy, S.M.; Ali, O.M.; Emselm, H.M.; Abdel-Rahman, A.A. Anticancer activity of new (tetrazol-5-yl) methylindole derivatives and their acyclic c-nucleoside analogs. Acta Pol. Pharm., 2012, 69, 669-677.
[37]
Jedhe, G.S.; Paul, D.; Gonnade, R.G.; Santra, M.K.; Hamel, E.; Nguyen, T.L.; Sanjayan, G.J. Correlation of hydrogen-bonding propensity and anticancer profile of tetrazole-tethered combretastatin analogues. Bioorg. Med. Chem. Lett., 2013, 23, 4680-4684.
[38]
El-Sayed, W.A.; El-Sofany, W.I.; Mohamed, A.M.; Flefel, E.M.; Awad, H.M. Synthesis and anticancer activity of new 1-thia-4-azaspiro[4.5]decane, their derived thiazolopyrimidine and 1,3,4-thiadiazole thioglycosides. Molecules, 2017, 22, 170-179.
[39]
Mohamed, A.M.; Al-Qalawi, H.M.; El-Sayed, W.A.; Arafa, W.A.A.; Alhumamais, M.S.; Hassan, A.K. Acta Poloniae Pharmaceutica. Drug Res. , 2015, 72(2), 307-318.
[40]
Flefel, E.M.; Tantawy, W.A.; El-Sayed, W.A.; Sayed, H.H.; Fathy, N.M. Synthesis and anticancer activity of new substituted pyrazoles and their derived 1,2,4-Triazoles and their sugar derivatives. J. Heterocycl. Chem., 2013, 50, 344-350.
[41]
El-Sayed, W.A.; El-Sofany, W.I. Mohamed, Hussein H.A.; Fathi, N.M. Synthesis and anticancer activity of new [(Indolyl) pyrazolyl] -1,3,4-oxadiazole thioglycosides and acyclic nucleoside analogs. Nucleosides Nucleotides Nucleic Acids, 2017, 46, 474-495.
[42]
El-Sayed, W.A.; Rashad, A.E.; Awad, S.M.; Ali, M.M. Synthesis and in vitro anti-tumor activty of some new substituted thio pyrimidines through radical balnce regulation. Nucleosides Nucleotides Nucleic Acids, 2009, 28, 261-274.
[43]
Abbas, E.M.H.; Amin, K.M.; El-Hamouly, W.S.; Dawood, D.H.; Abdalla, M.M. Synthesis, anti-inflammatory and antinociceptive activity of some novel benzothiazole derivatives. Res. Chem. Intermed., 2015, 41, 2537-2555.
[44]
Amine, E.W.S.; Mahmoud, K.; Abbas, E.M.; Abdel-Maguid, H.; Ali, E. Synthesis and antimicrobial activity of some 3-substituted 5,6-dimethoxy-2,3-dihydrobenzo[d]thiazol-2-one. Chin. J. Chem., 2009, 27, 1629-1634.
[45]
Hamdy, N.A.; Anwar, M.M.; Abu-Zied, K.M.; Awad, H.M. Synthesis, tumor inhibitory and antioxidant activity of new polyfunctionally 2-substituted 5,6,7,8-tetrahydronaphthalene derivatives containing pyridine, thioxopyridine and pyrazolopyridine moieties. Acta Poloniae Pharmaceutica-Drug Res., 2013, 70(6), 987-1001.
[46]
Soliman, H.A.; Yousif, M.N.M.; Said, M.M.; Hassan, N.A.; Ali, M.M.; Awad, H.M.; Abdel-Megeid, F.M.E. Synthesis of novel 1,6-naphthyridines, pyrano[3,2-c]pyridines and pyrido[4,3-d]pyrimidines derived from 2,2,6,6-tetramethylpiperidin-4-one for in vitro anticancer and antioxidant evaluatio. Der. Pharma Chem., 2014, 6(3), 394-410.
[47]
Awad, H.M.; Abd-Alla, H.I.; Mahmoud, K.H.; El-Toumy, S.A. In vitro anti-nitrosative, antioxidant, and cytotoxicity activities of plant flavonoids: A comparative study. Med. Chem. Res., 2014, 23(7), 3298-3307.
[48]
Staker, B.L.; Feese, M.D.; Cushman, M.; Pommier, Y.; Zembower, D.; Stewart, L.; Burgin, A.B. Structure of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex. J. Med. Chem., 2005, 48, 2336-2345.
Related Books
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Natural Product Chemistry
Therapeutic Use of Plant Secondary Metabolites
Therapeutic Implications of Natural Bioactive Compounds
Frontiers in Bioactive Compounds
Frontiers in Natural Product Chemistry
Frontiers in Natural Product Chemistry
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Natural Product Chemistry
Frontiers in Natural Product Chemistry
Article Metrics
36
3