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This work is licensed under a Creative Commons Attribution 4.0 International License.
Synthesis and Preliminary Anticancer Activity Study of New 6-Mercaptopurine Derivatives
Corresponding Author(s) : Dunya L. Al-Duhaidahawi
Asian Journal of Chemistry,
Vol. 30 No. 12 (2018): Vol 30 Issue 12
Abstract
The synthesis of asymmetrical disulfides is an essential alteration in progressive investigation in pharmaceutical chemistry. The current research pointed at the design and synthesis of novel antitumor products from 6-mercaptopurine by the introduction of heterocyclic substituted 1,2,4 triazole-sulfhydryl moiety as a bioisostere at SH group. To this functional group, a series of 12 s-triazole derivatives with different alkyl and aralkyl substituents as functionalized side chains of disulfide derivative were synthesized utilizing 1-chloro-benzotriazole as oxidizing agents. Structure of compounds was characterized by elemental microanalysis and spectral analysis followed by in vitro cytotoxic activities against CLL-119, L1210 and HL60 cell lines was assessed by MTT test method. The results from the primary test showed that the introduction of substituted 1,2,4-triazole-sulfhydryl highly improve the therapeutic efficacy of drug. Compounds 3, 5 and 8 show best anti-CCL-119 activity.
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- K. Schmiegelow, S.N. Nielsen, T.L. Frandsen and J. Nersting, J. Pediatr. Hematol. Oncol., 36, 503 (2014); https://doi.org/10.1097/MPH.0000000000000206.
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References
K. Schmiegelow, S.N. Nielsen, T.L. Frandsen and J. Nersting, J. Pediatr. Hematol. Oncol., 36, 503 (2014); https://doi.org/10.1097/MPH.0000000000000206.
B.A. Kamen, J. Pediatr. Hematol. Oncol., 31, 383 (2009); https://doi.org/10.1097/MPH.0b013e3181a6e191.
S.A. Coulthard, L.A. Hogarth, M. Little, E.C. Matheson, C.P.F. Redfern, L. Minto and A.G. Hall, Mol. Pharmacol., 62, 102 (2002); https://doi.org/10.1124/mol.62.1.102.
N.V. Bhagavan and C.-E. Ha, Essentials of Medical Biochemistry, edn 2, pp. 465-487 (2015).
J.H. Block and J.M. Beale, Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry, Lippincott Williams & Wilkins, edn 12, pp. 378-379 (2011).
O.H. Nielsen, B. Vainer and J. Rask-Madsen, Aliment. Pharmacol. Ther., 15, 1699 (2001); https://doi.org/10.1046/j.1365-2036.2001.01102.x.
I. Tiede, G. Fritz, S. Strand, D. Poppe, R. Dvorsky, D. Strand, H.A. Lehr, S. Wirtz, C. Becker, R. Atreya, J. Mudter, K. Hildner, B. Bartsch, M. Holtmann, R. Blumberg, H. Walczak, H. Iven, P.R. Galle, M.R. Ahmadian and M.F. Neurath, J. Clin. Invest., 111, 1133 (2003); https://doi.org/10.1172/JCI16432.
C. Cuffari, S. Hunt and T.M. Bayless, Aliment. Pharmacol. Ther., 14, 1009 (2000); https://doi.org/10.1046/j.1365-2036.2000.00812.x.
E. Raetz and J. Meyer, Hematologist, 13, 1 (2016).
K.K. Das, H.T. Nishino and A.T. Chan, Inflamm. Bowel Dis., 16, 1454 (2010); https://doi.org/10.1002/ibd.21205.
G.H. Elgemeie, Curr. Pharm. Des., 31, 2627 (2003); https://doi.org/10.2174/1381612033453677.
M. Arenas, G. Simpson and C.M. Lewis, Clin. Chem., 51, 2371 (2005); https://doi.org/10.1373/clinchem.2005.053157.
N.K. De Boer, A.A. van Bodegraven, B. Jharap, P. de Graaf and C.J. Mulder, Nat. Clin. Pract. Gastroenterol. Hepatol., 4, 686 (2007); https://doi.org/10.1038/ncpgasthep1000.
L.J. Derijks and D.R. Wong, Curr. Pharm. Des., 16, 145 (2010); https://doi.org/10.2174/138161210790112773.
K.B. Sloan, S.C. Wasdo and J. Rautio, Pharm. Res., 23, 2729 (2006); https://doi.org/10.1007/s11095-006-9108-0.
K.B. Sloan and S.C. Wasdo, ed.: M. Roberts and K. Walters, The Role of Prodrugs in Penetration Enhancement, In: Dermal Absorption and Toxicity Assessment, Marcel Dekker: New York, pp. 605–622 (2008).
D.R. Wong, L.J. Derijks, M.O. den Dulk, E.H. Gemmeke and P.M. Hooymans, Ther. Drug Monit., 29, 845 (2007); https://doi.org/10.1097/FTD.0b013e31815bf4dc.
R. Kaur, A.R. Dwivedi, B. Kumar and V. Kumar, Anticancer. Agents Med. Chem., 16, 465 (2016); https://doi.org/10.2174/1871520615666150819121106.
M. Galanski, V. Arion, M. Jakupec and B. Keppler, Curr. Pharm. Des., 9, 2078 (2003); https://doi.org/10.2174/1381612033454180.
Z. Li, Z. Gu, K. Yin, R. Zhang, Q. Deng and J. Xiang, Eur. J. Med. Chem., 44, 4716 (2009); https://doi.org/10.1016/j.ejmech.2009.05.030.
J. Lee, S.J. Kim, H. Choi, Y.H. Kim, I.T. Lim, H.M. Yang, C.S. Lee, H.R. Kang, S.K. Ahn, S.K. Moon, D.-H. Kim, S. Lee, N.S. Choi and K.J. Lee, J. Med. Chem., 53, 6337 (2010); https://doi.org/10.1021/jm1002414.
Y.B. Zhang, W. Liu, Y.S. Yang, X.L. Wang, H.L.Zhu, L.F. Bai and X.Y. Qiu, Med. Chem. Res., 22, 1 (2013).
K. Nepali, S. Sharma, R. Ojha and K.L. Dhar, Med. Chem. Res., 22, 1 (2013); https://doi.org/10.1007/s00044-012-0002-5.