iv) Precursors; Selective Inhibitory Activity Against Human Breast Cancer Cells, Positive to Estrogen Receptors">
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH FRONT

Structural and In Vitro Biological Studies of Organotin(iv) Precursors; Selective Inhibitory Activity Against Human Breast Cancer Cells, Positive to Estrogen Receptors

Vasilis I. Balas A , Christina N. Banti A B , Nikolaos Kourkoumelis C , Sotiris K. Hadjikakou A H , George D. Geromichalos D , Despina Sahpazidou D , Louise Male E , Mike B. Hursthouse E , Barbara Bednarz A F , Maciej Kubicki F , Konstantinos Charalabopoulos B G and Nick Hadjiliadis A H

A Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.

B Department of Experimental Physiology, Medical School, University of Ioannina, 45110 Ioannina, Greece.

C Medical Physics Laboratory, Medical School, University of Ioannina, 45110 Ioannina, Greece.

D Cell Culture, Molecular Modeling and Drug Design Laboratory, Symeonidion Research Center, Theagenion Cancer Hospital, 54007 Thessaloniki, Greece.

E Department of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK.

F Department of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznan, Poland.

G Department of Physiology, Democritus University Medical School, 68100 Alexandroupolis, Greece.

H Corresponding authors. Email: shadjika@uoi.gr, nhadjis@uoi.gr

Australian Journal of Chemistry 65(12) 1625-1637 http://dx.doi.org/10.1071/CH12448
Submitted: 28 September 2012  Accepted: 24 October 2012   Published: 26 November 2012

Abstract

Crystals of Ph3SnCl (1) were grown from a methanol/acetonitrile solution. Compounds [Ph3SnOH]n (2) and [(Ph2Sn)4Cl2O2(OH)2] (3) were crystallized from diethyl ether/methanol/acetonitrile and hot acetone/water solutions respectively, of the white precipitation, formed by adding KOH to solutions of 1 and [Ph2SnCl2] in 1 : 1 and 1 : 2 molar ratios respectively. Complex 1 was characterized by X-ray crystallography. X-ray structure determination of compounds 2 and 3 confirmed the previously reported identities. The molecular structure of 1, reported here, is a new polymorphic form of the known one for Ph3SnCl. Four independent [Ph3SnCl] molecules constitute the crystal structure of 1. The moieties are packed in two pairs in a tail-to-tail arrangement.

Complexes 13 were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (human cervical), MCF-7 (breast, estrogen receptor (ER) positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (kidney carcinoma), 786-O (renal adenocarcinoma), K1 (thyroid carcinoma), and the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) versus, the normal immortalized human mammary gland epithelial cell line MTSV17 with a sulforhodamine B (SRB) assay. The results show potent cytotoxic activity of the complexes against all cell lines used, which was superior to that of cisplatin (CDDP). Compounds 13 showed higher activity against breast cancer cells MCF-7 (ER positive) than against of MDA-MB-231 (ER negative). These findings prompted us to search for possible interaction of these complexes with other cellular elements of fundamental importance in cell proliferation. The influence of these complexes 13 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX), as well as their binding affinity towards calf thymus-DNA, were kinetically and theoretically studied.

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References

[1]  (a) B. A. Buck-Koehntop, F. Porcelli, J. L. Lewin, C. J. Cramer, G. Veglia, J. Organomet. Chem. 2006, 691, 1748.
         | CrossRef | 1:CAS:528:DC%2BD28XislCns74%3D&md5=50f8ed669fa57b716f865ef72248a383CAS | open url image1
      (b) K. E. Appel, Drug Metab. Rev. 2004, 36, 763.
         | CrossRef | open url image1

[2]     (a) “R.E.D. Facts: Triphenyltin Hydroxide”, EPA-738-F-99–014, November 1999 (US EPA).
         (b) A. G. Davies, Organotin Chemistry 2004 (Wiley-VCH: Weinheim).

[3]  M. Gajda, A. Jancso, “Organotins, formation, use, speciation and toxicology”, Metal Ions in Life Sciences 2010, Ch 7 (RSC Publishing: Cambridge).

[4]  (a) M. S. Rose, Biochem. J. 1969, 111, 129.
         | 1:CAS:528:DyaF1MXlsVShtg%3D%3D&md5=c028ba3ae2293f158acbd2d6fc7f3dc8CAS | open url image1
      (b) B. M. Elliott, W. N. Aldridge, Biochem. J. 1977, 163, 583. open url image1
      (c) K. R. Siebenlist, F. Taketa, Biochem. J. 1986, 233, 471. open url image1
      (d) G. Zolese, R. Gabbianelli, G. C. Caulini, E. Bertoli, G. Falcioni, Proteins 1999, 34, 443.
         | CrossRef | open url image1

[5]  (a) W. N. Aldridge, B. W. Street, Biochem. J. 1970, 118, 171.
         | 1:CAS:528:DyaE3cXks1Cmurs%3D&md5=eb36e8018ee2f66444cd196ba47b3e1fCAS | open url image1
      (b) K. Cain, D. E. Griffiths, Biochem. J. 1977, 162, 575. open url image1
      (c) A. P. Dawson, M. J. Selwyn, Biochem. J. 1974, 138, 349. open url image1
      (d) A. P. Dawson, B. G. Farrow, M. J. Selwyn, Biochem. J. 1982, 202, 163. open url image1
      (e) M. S. Rose, E. A. Lock, Biochem. J. 1970, 120, 151. open url image1

[6]  D. K. Apps, C. W. Lorna, Biochem. Biophys. Res. Commun. 1996, 227, 839.
         | CrossRef | 1:CAS:528:DyaK28XmtlKnsb4%3D&md5=914f60b9f9ce6e441624e479d229bfc7CAS | open url image1

[7]  (a) J. J. Chicano, J. Ortiz, J. A. Teruel, F. J. Aranda, Biochim. Biophys. Acta 2001, 1510, 330.
         | CrossRef | 1:CAS:528:DC%2BD3MXpsFGrsA%3D%3D&md5=003e28723dfc95533dd703abee04f6daCAS | open url image1
      (b) J. Sarapuk, H. Kleszczynska, S. Przestalski, Appl. Organomet. Chem. 2000, 14, 40.
         | CrossRef | open url image1

[8]  (a) Z. Yang, T. Bakas, A. Sanchez-Diaz, K. Charalabopoulos, J. Tsangaris, N. Hadjiliadis, J. Inorg. Biochem. 1998, 72, 133.
         | CrossRef | 1:CAS:528:DyaK1MXhs12lsbc%3D&md5=b0f82d858f6e26cacf6fd7c1e335b56bCAS | open url image1
      (b) L. Ghys, M. Biesemans, M. Gielen, A. Garoufis, N. Hadjiliadis, R. Willem, J. C. Martins, Eur. J. Inorg. Chem. 2000, 513.
         | CrossRef | open url image1
      (c) L. Nagy, B. Gyurcsik, K. Burger, S. Yamashita, T. Yamaguchi, H. Wakita, M. Nomura, Inorg. Chim. Acta 1995, 230, 105.
         | CrossRef | open url image1
      (d) L. Nagy, T. Yamaguchi, K. Yoshida, Struct. Chem. 2003, 14, 77.
         | CrossRef | open url image1
      (e) L. Nagy, A. Szorcsik, J. Inorg. Biochem 2002, 89, 1.
         | CrossRef | open url image1
      (f) L. Nagy, T. Yamaguchi, K. Yoshida, Struct. Chem. 2003, 14, 77.
         | CrossRef | open url image1
      (g) H. Baratne-Jankovics, I. Nagy, L. Pellerito, N. Buzas, R. Barbieri, J. Inorg. Chem. 2002, 92, 55. open url image1
      (h) A. Jancso, L. Nagy, E. Moldrheim, E. Sletten, J. Chem. Soc., Dalton Trans. 1999, 1587.
         | CrossRef | open url image1

[9]  (a) K. Fent, Crit. Rev. Toxicol. 1996, 26, 3.
         | CrossRef | open url image1
      (b) K. R. Siebenlist, F. Taketa, Biochem. J. 1986, 233, 471. open url image1
      (c) H. Stridh, I. Cotgreave, M. Muller, S. Orrenius, D. Gigliotti, Chem. Res. Toxicol. 2001, 14, 791.
         | CrossRef | open url image1

[10]  (a) S. K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev. 2009, 253, 235.
         | CrossRef | 1:CAS:528:DC%2BD1cXhsVWhsL%2FK&md5=0067d3ae6d568b1b9791695a93f56d98CAS | open url image1
         (b) Tin compounds and their therapeutic potential, Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine (Eds M. Gielen, E. R. T. Tiekink) 2005 (John Wiley & Sons: Chichester).
      (c) A. K. Saxena, F. Huber, Coord. Chem. Rev. 1989, 95, 109.
         | CrossRef | open url image1

[11]  (a) S. Tabassum, C. Pettinari, J. Organomet. Chem. 2006, 691, 1761.
         | CrossRef | 1:CAS:528:DC%2BD28XislCns7w%3D&md5=0da2e6974d54ccbbe787a66dbb279994CAS | open url image1
      (b) C. Pellerito, P. D’Agati, T. Fiore, C. Mansueto, V. Mansueto, G. Stocco, L. Nagy, L. Pellerito, J. Inorg. Biochem. 2005, 99, 1294.
         | CrossRef | open url image1
      (c) F. Cima, L. Ballarin, Appl. Organomet. Chem. 1999, 13, 697.
         | CrossRef | open url image1

[12]  (a) M. N. Xanthopoulou, S. K. Hadjikakou, N. Hadjiliadis, M. Kubicki, S. Karkabounas, K. Charalabopoulos, N. Kourkoumelis, T. Bakas, J. Organomet. Chem. 2006, 691, 1780.
         | CrossRef | 1:CAS:528:DC%2BD28XislCns7s%3D&md5=4c314ffee99d128d7b7c538da76d829cCAS | open url image1
      (b) M. N. Xanthopoulou, S. K. Hadjikakou, N. Hadjiliadis, M. Schurmann, K. Jurkschat, A. Michaelides, S. Skoulika, T. Bakas, J. Binolis, S. Karkabounas, K. Charalabopoulos, J. Inorg. Biochem. 2003, 96, 425.
         | CrossRef | open url image1
      (c) M. N. Xanthopoulou, S. K. Hadjikakou, N. Hadjiliadis, E. R. Milaeva, J. A. Gracheva, V.-Y. Tyurin, N. Kourkoumelis, K. C. Christoforidis, A. K. Metsios, S. Karkabounas, K. Charalabopoulos, Eur. J. Med. Chem. 2008, 43, 327.
         | CrossRef | open url image1
      (d) M. N. Xanthopoulou, S. K. Hadjikakou, N. Hadjiliadis, M. Kubicki, S. Skoulika, T. Bakas, M. Baril, I. S. Butler, Inorg. Chem. 2007, 46, 1187.
         | CrossRef | open url image1

[13]  (a) V. I. Balas, I. I. Verginadis, G. D. Geromichalos, N. Kourkoumelis, L. Male, M. B. Hursthouse, K. H. Repana, E. Yiannaki, K. Charalabopoulos, T. Bakas, S. K. Hadjikakou, Eur. J. Med. Chem. 2011, 46, 2835.
         | CrossRef | 1:CAS:528:DC%2BC3MXmsVOku7Y%3D&md5=e496eba6217ee7b09aae06c22a7d3a85CAS | open url image1
      (b) V. I. Balas, S. K. Hadjikakou, N. Hadjiliadis, N. Kourkoumelis, M. E. Light, M. Hursthouse, A. K. Metsios, S. Karkabounas, Bioinorganic Chem. Applic. 2008,
         | CrossRef | open url image1
      (c) D. B. Shpakovsky, C. N. Banti, G. Beaulieu-Houle, N. Kourkoumelis, M. Manoli, M. J. Manos, A. J. Tasiopoulos, S. K. Hadjikakou, E. R. Milaeva, K. Charalabopoulos, T. Bakas, I. S. Butler, N. Hadjiliadis, Dalton Trans. 2012,
         | CrossRef | open url image1

[14]  (a) L. Rocamora-Reverte, E. Carrasco-Garc, J. Ceballos-Torres, S. Prashar, G. N. Kaluderovic, J. A. Ferragut, S. Gomez-Ruiz, ChemMedChem 2012, 7, 301.
         | CrossRef | 1:CAS:528:DC%2BC3MXhs1SgurvN&md5=13cd858a1973e887a2f45dea4e3909acCAS | open url image1
      (b) A. Ortiz, J. A. Teruel, F.J. Aranda, Biochimica et Biophysica Acta 2005, 1720, 137.
         | CrossRef | open url image1
      (c) G. Pavlakovic, M. D. Kane, C. L. Eyer, A. Kanthasamy, G. E. Isom, J. Neurochem. 1995, 65, 2338.
         | CrossRef | open url image1

[15]  A. Kafer, H. F. Krug, Environ. Health Perspect. 1994, 3, 325. open url image1

[16]  (a) B. Samuelsson, S. E. Dahlen, J. Lindgren, C. A. Rouzer, C. N. Serhan, Science 1987, 237, 1171.
         | CrossRef | 1:CAS:528:DyaL2sXls1yrsb4%3D&md5=19e2b912c132d17ea9278bbbc08013eaCAS | open url image1
      (b) M. J. Knapp, J. P. Klinman, Biochemistry 2003, 42, 11466.
         | CrossRef | open url image1
      (c) X.-Z. Ding, C. A. Kuszynski, T. H. El-Metwally, T. E. Adrian, Biochem. Biophys. Res. Commun. 1999, 266, 392.
         | CrossRef | open url image1

[17]  (a) N. G. Bokii, G. N. Zakharova, Yu. T. Struchkov, J. Struct. Chem. 1970, 11, 247.
         | CrossRef | open url image1
      (b) J. S. Tse, F. L. Lee, E. J. Gabe, Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 1986, 42, 1876. open url image1
      (c) S. Weng Ng, Acta Crystallogr Sect. C: Cryst. Struct. Commun. 1995, 51, 2292.
         | CrossRef | open url image1

[18]  (a) C. Glidewell, D. C. Liles, Acta Crystallogr. B 1978, 34, 129.
         | CrossRef | open url image1
      (b) C. Glidewell, J. N. Low, J. A. S. Bomfim, C. A. L. Filgueiras, J. L. Wardell, Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 2002, 58, m199.
         | CrossRef | open url image1
      (c) C.-x. Fu, J.-h. Zhang, C.-l. Ma, Z.-t. Zhang, Chin. J. Synth. Chem. 2003, 11, 189. open url image1

[19]  (a) J. F. Vollano, R. O. Day, R. R. Holmes, Organometallics 1984, 3, 745.
         | CrossRef | 1:CAS:528:DyaL2cXitFSjsLc%3D&md5=2f16c541b949e996823e87deab4547d1CAS | open url image1
      (b) E. R. T. Tiekink, Acta Crystallogr., Sect. C. Cryst. Struct. Commun. 1991, 47, 661.
         | CrossRef | open url image1
      (c) R. A. Kresinski, R. J. Staples, J. P. Fackler, Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 1994, 50, 40. open url image1
      (d) M. J. Cox, E. R. Tiekink, Z. Kristallogr. 1994, 209, 622.
         | CrossRef | open url image1

[20]  (a) V. Boudnitskaya, I. G. Borisova, FEBS Lett. 1972, 24, 359.
         | CrossRef | open url image1
      (b) F. Husson, Y. Pagot, S. Kermasha, J. M. Belin, Enzyme Microb. Technol. 1998, 23, 42.
         | CrossRef | open url image1

[21]  I. I. Ozturk, A. K. Metsios, S. Filimonova-Orlova, N. Kourkoumelis, S. K. Hadjikakou, M. Manos, A. J. Tasiopoulos, S. Karkabounas, E. R. Milaeva, N. Hadjiliadis, Med. Chem. Res. 2012, 21, 3523.
         | CrossRef | 1:CAS:528:DC%2BC3MXhsV2lsLrM&md5=0af810d0f4dd16a7b3a41edff0687d2bCAS | open url image1

[22]  (a) C. N. Banti, A. D. Giannoulis, N. Kourkoumelis, A. M. Owczarzak, M. Poyraz, M. Kubicki, K. Charalabopoulos, S. K. Hadjikakou, Metallomics 2012, 4, 545.
         | CrossRef | 1:CAS:528:DC%2BC38XnvVOns7c%3D&md5=8c7edc52faf41359603341069d5cc15aCAS | open url image1
      (b) C. N. N’soukpoe-Kossi, C. Descoteaux, E. Asselin, H. A. Tajmir-Riahi, G. Berube, DNA Cell Biol. 2008, 27, 101.
         | CrossRef | open url image1

[23]  H. Niyazi, J. P. Hall, K. O’Sullivan, G. Winter, T. Sorensen, J. M. Kelly, C. J. Cardin, Nat. Chem. 2012, 4, 621.
         | CrossRef | 1:CAS:528:DC%2BC38XovFyrt7c%3D&md5=a01f62ee41cf83beb956745086c450ccCAS | open url image1

[24]  M. H. Hanigan, P. Devarajan, Cancer Ther. 2003, 1, 47. open url image1

[25]     (a) G. M. Sheldrick, University of Göttingen, Germany 1997.
      (b) M. C. Burla, R. Caliandro, B. Carrozzini, G. Cascarano, L. De Caro, C. Giacovazzo, G. Polidori, J. Appl. Cryst. 2004, 37, 258.
         | CrossRef | open url image1

[26]     (a) A. Gorman, J. McCarthy, D. Finucane, W. Reville, T. Cotter, Techniques in Apoptosis. A User’s Guide (Eds T. G. Cotter, S. J. Martin) 1996, pp. 6 (Portland Press Ltd: London, UK).
      (b) P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J. T. Warren, H. Bokesch, S. Kenney, M. R. Boyd, J. Natl. Cancer Inst. 1990, 82, 1107.
         | CrossRef | open url image1
      (c) K. T. Papazisis, G. D. Geromichalos, K. A. Dimitriadis, A. H. Kortsaris, J. Immunol. Methods 1997, 208, 151.
         | CrossRef | open url image1

[27]  (a) R. Thomsen, M. H. Christensen, J. Med. Chem. 2006, 49, 3315.
         | CrossRef | 1:CAS:528:DC%2BD28XjvFyiu7w%3D&md5=fa7ba8e130b50c50c348441db57ddedaCAS | open url image1
      (b) R. Abagyan, M. Totrov, J. Mol. Biol. 1994, 235, 983.
         | CrossRef | open url image1
      (c) R. Abagyan, M. Totrov, D. Kuznetsov, J. Comput. Chem. 1994, 15, 488.
         | CrossRef | open url image1
      (d) G. Nemethy, K. D. Gibson, K. A. Palmer, C. N. Yoon, G. Paterlini, A. Zagari, S. Rumsey, H. A. Scheraga, J. Phys. Chem. 1992, 96, 6472.
         | CrossRef | open url image1



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