Copper thiosemicarbazones: Antiproliferative action against C6 glioma cells

Authors

  • Qiang Fu Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000
  • Zhi-Yu Gao Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000
  • Jie Zhang Liaocheng People's Hospital
  • Han-Yu Sun Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000
  • Chao Liu Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000
  • Jin-Hong Ren Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000

DOI:

https://doi.org/10.3329/bjp.v9i4.19772

Keywords:

Copper, Glioma, Thiosemicarbazones

Abstract

2(E)-2-[1-(4-pyridinyl)ethylidene]hydrazinecarbothioammidehydrochloride (1) and two of its copper complexes were synthesized and structurally characterized. Cu(I) polymeric complex {[Cu(SCN)(3-Acpy)2]}n (2) was synthesized by in situ mixing of Cu(BF4)2.6H2O, 4-acetylpyridine (4-Acpy) and semicarbazide whereas a dinuclear Cu(II) complex (3) was obtained from the reaction of Cu(BF4)2.6H2O, 4-acetylpyridine and ammonium thiocyanate. Magnetic measurements were performed for the dinuclear complex. All the thiosemicarbazones were cytotoxic against malignant RT2 glioblastoma cells (expressing p53 protein) with IC50 values in the 5.1-13.2 µM range, and against malignant T98 glioblastoma cells (expressing mutant p53 protein) with IC50 values in the 4.5-31 µM range. Coordination to copper strongly increased the cytotoxic potential in complexes 2 and 3, when compared to that of free ligand and were found to be more potent than cisplatin. All the test compounds (1-3) were able to induce cell death by apoptosis.

Downloads

Download data is not yet available.
Abstract
308
Download
139 Read
159

References

Arion VB, Jakupec MA, Galanski M, Unfried P, Keppler BK. Synthesis, structure, spectroscopic and in vitro antitumour studies of a novel gallium(III) complex with 2-acetylpyridine (4)N-dimethylthiosemicarbazone. J Inorg Biochem. 2002; 91: 298-305.

Chi YH, Yu L, Shi JM, Zhang YQ, Hu TQ, Zhang GQ, Shi W, Cheng P. ?-? Stacking and ferromagnetic coupling mechanism on a binuclear Cu(II) complex. Dalton Trans. 2011; 40: 1453-62.

Cobeljic B, Pevec A, Turel I, Swart M, Mitic D, Milenkovic M, Markovic I, Jovanovic M, Sladic D, Jeremic M, Andelkovic K. Synthesis, characterization, DFT calculations and biological activity of derivatives of 3-acetylpyridine and the zinc(II) complex with the condensation product of 3-acetylpyridine and semicarbazide. Inorg Chim Acta. 2013; 404: 5-12.

Dai C, Holland EC. Glioma models. Biochim Biophys Acta. 2001; 1551: M19-M27.

Enari M, Sakahira H,Yokoyama H, Okawa K, Iwamatsu A, Nagata S. A caspase-activated Dnase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 1998; 391: 43-50.

Fisher D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T. In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 2003; 24: 1121-31.

Fondo M, Garcia-Deibe AM, Corbella M, Ruiz E, Tercero J, Sanmartin J,Bermejo MR. Unexpected ferromagnetic interaction in a new tetranuclear copper(II) complex: Synthesis, crystal structure, magnetic properties, and theoretical studies. Inorg Chem. 2005; 44: 5011-20.

Fondo M, Ocampo N, Garcia-Deibe AM, Corbella M, Bermejo MR, Sanmartin J. Ferromagnetism in dinuclear copper(II)-phenolate complexes with exogenous O-donor bridges: A comparative study. Dalton Trans. 2005; 3785-94.

Freshney RI. Culture of animal cells: A manual of basic technique. 4th ed. Wiley Liss, 2000.

Graminha AE, Rodrigues C, Batista AA, Teixeira LR, Fagundes ES, Beraldo H. Ruthenium(II) complexes of 2-benzoylpyridine-derived thiosemicarbazones with cytotoxic activity against human tumor cell lines. Spectrochim Acta Part A: Mol Biomol Spectrosc. 2008; 69: 1073-76.

Hosli AP, Sappino N, De Tribolet, Dietrich PY. Malignant glioma: Should chemotherapy be overthrown by experimental treatments? Ann Oncol. 1996; 9: 589-600.

Jones RA, Cheung CY, Black FE, Zia JK, Stayton PS, Hoffman AS, Wilson MR.Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pH-sensitive disruption of endosomal vesicles. Biochem J. 2003; 372: 65-75.

Khanpour M, Morsali A. Solid state crystal-to-crystal transformation from a monomeric structure to 1-D coordination polymers on anion exchange. Cryst Eng Comm. 2009; 11: 2585-87.

Kowol CR, Berger R,Eichinger R, Roller A, Jakupec MA, Schmidt PP, Arion VB, Keppler BK. Gallium(III) and iron(III) complexes of alpha-N-heterocyclic thiosemicarbazones: synthesis, characterization, cytotoxicity, and interaction with ribonucleotide reductase. J Med Chem. 2007; 50: 1254-65.

Levin VA, Gutin PH, Leibel S ,Vita VTD, Hellman S, Rosenberg AS. Cancer: Principles and Practice of Oncology, Lippincott, Philadelphia, 1993, 1697-737.

Liberta AE, West DX. Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: current status.Biometals 1992; 5: 121-26

Ma Y, Gao DZ, Zhang W, Yoshimura K, Liao DZ, Jiang ZH, Yan SP. A novel copper(II)-radical complex with ferro-magnetic interaction: synthesis, crystal structure and magnetic properties. Inorg Chim Acta. 2006; 359: 4655-59.

Mena A, Bastos B, da Silva JG, da Maia PIDS, Deflon VM, Batista AA, Ferreira AVM, Botion LM, Niquet E, Beraldo H. Oxovanadium(IV) and (V) complexes of acetylpyridine-derived semicarbazones exhibit insulin like activity. Polyhedron 2008; 27: 1787-94.

Miller MC III, Stineman CN, Vance JR, West DX, Hall IH. H. Multiple mechanisms for cytotoxicity induced by copper(II) complexes of 2-acetylpyrazine-N-substituted thiosemi-carbazones. J Appl Organometal Chem. 1999; 13: 9-19.

Nakamoto K. Infrared and Raman spectra of inorganic and coordination compounds. 5th ed. New York, John Wiley & Sons Inc., 1997.

O´Connor PM, Jackman J, Bae I,Myers TG, Fan S, Mutoh M, Scudiero DA, Monks A, Sausville EA, Weinstein JN, Friend S, Fornace AJ, Kohn KW. Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. Cancer Res. 1997; 57: 4285-300.

Paul S, Nanda PK, Mathoniere C, Hearns NGR, Clerac R, Ray D. Aqua bridge cleavage and metal ion extrusion by thiocyanate anions in a dicopper complex. Inorg Chim Acta. 2011; 370: 108-16.

West DX, Padhye S, Sonawane PB. Structural and physical correlation in the biological properties of transition metal N-heterocyclic thiosemicarbazones and S-alkyldithiocarbazate complexes. Struct. Bond. 1991; 76: 1-50.

Downloads

Additional Files

Published

2014-10-01

How to Cite

Fu, Q., Z.-Y. Gao, J. Zhang, H.-Y. Sun, C. Liu, and J.-H. Ren. “Copper Thiosemicarbazones: Antiproliferative Action Against C6 Glioma Cells”. Bangladesh Journal of Pharmacology, vol. 9, no. 4, Oct. 2014, pp. 466-73, doi:10.3329/bjp.v9i4.19772.

Issue

Vol. 9 No. 4 (2014)

Section

Research Articles

License

Authors who publish with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).