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Synthesis and Anticancer Properties of Silver(I) Complexes Containing 2,6-Bis(substituted)pyridine Derivatives

DOI: 10.1155/2013/256836

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Several new 2,6-bis(substituted)pyridine ligands and 2,6-bis(substituted)pyridine Ag(I) nitrate complexes were synthesized and characterized spectroscopically. The newly synthesized ligands include pyridine-2,6-bis(3-oxopropanenitrile) (1), pyridine-2,6-bis(2-cyano-N-phenyl-3-oxopropanethioamide) (2), and pyridine-2,6-bis((E)-2-(2-phenylhydrazono)-3-oxopropanenitrile) (3). The newly synthesized ligands and silver(I) complexes were evaluated for their in vitro anticancer activity against four human cancer cell lines including hepatocellular carcinoma (HePG2), lung adenocarcinoma (A549), colon carcinoma (HT29), and breast adenocarcinoma (MCF7). Most of the newly synthesized silver(I) complexes exhibited better activity than the ligands, and the results have been compared with doxorubicin as a reference drug. 1. Introduction Chemical and biological activity of the organic complexes is not possessed only by the metal or organic ligand but also this activity can be fine-tuned by subtle changes in the electronic and steric properties of the complexes or by variation of the oxidation state of the metal. These features provide a versatile platform for drug design that is now being exploited in several areas. For centuries, silver compounds have been known to possess interesting biological properties that show potent antibacterial properties [1–4]. Also, they were popular remedies for tetanus and rheumatism in the 19th century and for colds and gonorrhea before the advent of antibiotics in the early part of the 20th century [5]. Additionally, silver compounds used for treating mental illness, epilepsy, and nicotine addiction [6, 7]. Furthermore, silver compounds have reemerged as a viable treatment option for infections encountered in burns, open wounds, and chronic ulcers [8–11]. On the other hand, functionalized pyridine derivatives are gaining a great deal of interest in medicinal and organic synthesis, where some of pyridine derivatives are used as bactericides [12], fungicides [13], and anticancer agents [14–17]. In view of these observations and in continuation of our current interest in the synthesis of organic compounds for biological evaluations [18–25] and our interest in the chemistry of 2,6-disubstituted pyridine derivatives [26–29], we described herein a facile synthesis of novel silver complex with some of the newly synthesized 2,6-disubstituted pyridine ligands. The newly synthesized compounds were evaluated for their in vitro anticancer activity against four human cancer cell lines including hepatocellular carcinoma (HePG2), lung adenocarcinoma


[1]  J. B. Wright, D. L. Hansen, and R. E. Burrell, “The comparative efficacy of two antimicrobial barrier dressings: in vitro examination of two controlled release of silver dressings,” Wounds, vol. 10, no. 6, pp. 179–188, 1998.
[2]  J. W. Richard, B. A. Spencer, L. F. McCoy, et al., “Acticoat versus Silverlon: the truth,” Journal of Burns and Surgical Wound Care, vol. 1, no. 1, pp. 11–19, 2002.
[3]  A. D. Russell and W. B. Hugo, “7 antimicrobial activity and action of silver,” Progress in Medicinal Chemistry, vol. 31, pp. 351–370, 1994.
[4]  F. Fu-Ren and J. F. Allen, “Chemical, electrochemical, gravimetric, and microscopic studies on antimicrobial silver films,” The Journal of Physical Chemistry B, vol. 106, no. 2, pp. 279–287, 2002.
[5]  S. M. Mirsattari, R. R. Hammond, M. D. Sharpe, F. Y. Leung, and G. B. Young, “Myoclonic status epilepticus following repeated oral ingestion of colloidal silver,” Neurology, vol. 62, no. 8, pp. 1408–1410, 2004.
[6]  M. R. Alidaee, A. Taheri, P. Mansoori, and S. Z. Ghodsi, “Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial,” British Journal of Dermatology, vol. 153, no. 3, pp. 521–525, 2005.
[7]  F. Tanweer and J. Hanif, “Re: silver nitrate cauterisation, does concentration matter?” Clinical Otolaryngology, vol. 33, no. 5, pp. 503–504, 2008.
[8]  B. G. A. Lansdown, “The role of silver.,” European Tissue Repair Society Bulletin. In press.
[9]  J. B. Wright, K. Lam, A. G. Buret, M. E. Olson, and R. E. Burrell, “Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing,” Wound Repair Regeneration, vol. 10, no. 3, pp. 141–151, 2002.
[10]  H. N. Paddock, G. S. Schultz, and K. J. Perrin, “Clinical assessment of silver-coated antimicrobial dressing on MMPs and cytokine levels in non-healing wounds,” in Proceedings of the Annual Meeting of the Wound Healing Society, Baltimore, Md, USA, July 2002.
[11]  H. Wu and H., “Synthesis, structure, DNA-binding properties and antioxidant activity of silver(I) complexes containing V-shaped bis-benzimidazole ligands,” Dalton Transactions, vol. 41, no. 29, pp. 8829–8838, 2012.
[12]  G. Malicorne, J. Bompart, L. Giral, and E. Despaux, “Synthesis and antibacterial activity of 4,7-dihydro-4-ethyl-7-oxothieno(3,2-b)pyridine-6-carboxylic acids,” European Journal of Medicinal Chemistry, vol. 26, no. 1, pp. 3–11, 1991.
[13]  S. L. Hargreaves, B. L. Pilkington, S. E. Russell, and P. A. Worthington, “The synthesis of substituted pyridylpyrimidine fungicides using palladium-catalysed cross-coupling reactions,” Tetrahedron Letters, vol. 41, no. 10, pp. 1653–1656, 2000.
[14]  E. Szoko and T. Tabi, “Analysis of biological samples by capillary electrophoresis with laser induced fluorescence detection,” Journal of Pharmaceutical and Biomedical Analysis, vol. 53, no. 5, pp. 1180–1192, 2010.
[15]  H. Zhao, L. Shi, J. Q. Cao, W. Li, X. Wen, and Y. Q. Zhao, “A new triterpene saponin from Panax japonicus C. A. Meyer var major (Burk.) C. Y. Wu et K. M. Feng,” Chinese Chemical Letters, vol. 21, no. 10, pp. 1216–1218, 2010.
[16]  B. K. Banik and F. F. Becker, “Novel 6,12-disubstituted chrysene as potent anticancer agent: synthesis, in vitro and in vivo study,” European Journal of Medicinal Chemistry, vol. 45, no. 10, pp. 4687–4691, 2010.
[17]  M. T. Rodrigues, J. C. Gomes, J. Smith, and F. Coelho, “Simple and highly diastereoselective access to 3,4-substituted tetrahydro-1,8-naphthyridines from Morita-Baylis-Hillman adducts,” Tetrahedron Letters, vol. 51, no. 38, pp. 4988–4990, 2010.
[18]  G. Mlostoń, A. Pieczonka, K. A. Ali, A. Linden, and H. Heimgartner, “A new approach to morpholin-2-one derivatives via the reaction of β-amino alcohols with dicyanofumarates,” Arkivoc, pp. 181–192, 2012.
[19]  A. M. Farag, A. S. Mayhoub, T. M. Abdalla et al., “Synthesis and structure-activity relationship studies of pyrazole-based heterocycles as antitumor agents,” Archiv der Pharmazie, vol. 343, no. 7, pp. 384–396, 2010.
[20]  A. E. Amr, K. A. Ali, and M. M. Abdalla, “Cytotoxic, antioxidant activities and structure activity relationship of some newly synthesized terpenoidal oxaliplatin analogs,” European Journal of Medicinal Chemistry, vol. 44, no. 2, pp. 901–907, 2009.
[21]  A. M. Farag, Y. M. Elkholy, and K. A. Ali, “Regioselective synthesis of diazaspiro[4.4]nona- and tetrazaspiro[4.5]deca-2,9-diene-6-one derivatives,” Journal of Heterocyclic Chemistry, vol. 45, no. 1, pp. 279–283, 2008.
[22]  S. A. Ghozlan, A. A. Mohammed, A. E. Amr, K. A. Ali, and A. A. Abd El-Wahab, “Synthesis and antimicrobial activity of some heterocyclic 2,6-bis(substituted)-1,3,4-thiadiazolo-, oxadiazolo-, and oxathiazolidino-pyridine derivatives from 2,6-pyridine dicarboxylic acid dihydrazide,” Journal of Heterocyclic Chemistry, vol. 48, no. 5, pp. 1103–1110, 2011.
[23]  K. A. Ali, E. A. Ragab, T. A. Farghaly, and M. M. Abdalla, “Synthesis and structure-activity relationship studies of pyrazole-based heterocycles as antitumor agents,” Acta Poloniae Pharmaceutica, vol. 68, pp. 237–247, 2011.
[24]  A. M. Farag, K. A. K. Ali, T. M. A. El-Debss et al., “Design, synthesis and structure-activity relationship study of novel pyrazole-based heterocycles as potential antitumor agents,” European Journal of Medicinal Chemistry, vol. 45, no. 12, pp. 5887–5898, 2010.
[25]  K. A. Ali, H. M. Hosni, E. A. Ragab, and S. I. Abd El-Moez, “Synthesis and antimicrobial evaluation of some new cyclooctanones and cyclooctane-based heterocycles,” Archiv der Pharmazie, vol. 345, pp. 231–239, 2012.
[26]  K. A. Ali, “A new convenient synthesis of some novel 2,6-disubstituted-pyridine derivatives,” Arkivoc, vol. 2010, no. 11, pp. 55–63, 2010.
[27]  K. A. Ali, M. A. Elsayed, and H. S. Abdalghfar, “Synthesis and reactions of 2,6-bis[3-oxo-3-propanenitrile-2-(N, N-dimethylamino) methylene]pyridine,” Arkivoc, vol. 2011, no. 2, Article ID 37179, 2010.
[28]  K. A. Ali, M. A. Elsayed, and A. M. Farag, “Synthesis of some new pyridine-2,6-bis-heterocycles,” Heterocycles, vol. 85, no. 8, pp. 1913–1923, 2012.
[29]  K. A. Ali, “Synthesis of pyridine-2,6-bis-((E)-2-benzylidene-3-oxopropanenitrile) and Its behavior towards nitrogen binucleophiles,” Heterocycles, vol. 85, no. 8, pp. 1975–1986, 2012.
[30]  M. T. Casey, P. Guinan, A. Canavan, M. McCann, C. Cardin, and N. B. Kelly, “Reaction of 1,1'-diacetylferrocene with hydrazine hydrate: synthesis and X-ray crystal structures of bis(hydrazine)bis(hydrazinecarboxylato-N',O)iron(II), [Fe(N2H4)2(O2CNHNH2)2], and the cyclic biferrocene diazine, [N(Me)CC5H4FeC5H4C(Me)N]2,” Polyhedron, vol. 10, no. 4-5, pp. 483–489, 1991.
[31]  M. M. Abd-Elzaher, “Synthesis and spectroscopic characterization of some tetradentate Schiff bases and their nickel, copper and zinc complexes,” Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, vol. 30, no. 9, pp. 1805–1816, 2000.
[32]  S. Sarawat, G. S. Srivastava, R. C. Mehrotra, and R. C., “Schiff base complexes of organotin(IV). Reactions of trialkyltin(IV) chlorides and alkoxides with N-substituted salicylideneimines,” Journal of Organometallic Chemistry, vol. 129, no. 2, pp. 155–161, 1977.
[33]  M. M. Abd-Elzaher, “Synthesis and spectroscopic characterization of some ferrocenyl Schiff bases containing pyridine moiety and their complexation with cobalt, nickel, copper and zinc,” Journal of the Chinese Chemical Society, vol. 51, pp. 499–504, 2004.
[34]  T. Mosmann, “Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays,” Journal of Immunological Methods, vol. 65, no. 1-2, pp. 55–63, 1983.
[35]  B. S. El-Menshawi, W. Fayad, K. Mahmoud et al., “Screening of natural products for therapeutic activity against solid tumors,” Indian Journal of Experimental Biology, vol. 48, no. 3, pp. 256–264, 2010.


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