Crystal structures and in vitro anticancer studies on new unsymmetrical copper(II) Schiff base complexes derived from meso-1,2-diphenyl-1,2-ethylenediamine: a comparison with related symmetrical ones

Abstract Two new unsymmetrical copper(II) Schiff base complexes, [CuLn(py)]ClO4 (n = 1, 2) in which Ln represents a tridentate N2O type Schiff base ligand, were synthesized. Lns were derived from monocondensation of meso-1,2-diphenyl-1,2-ethylenediamine with salicylaldehyde or 3-methoxysalicylaldehyde. The reaction between [CuLn(py)]ClO4 and other salicylaldehyde derivatives resulted in new N2O2 unsymmetrical tetradentate CuII complexes, CuL3–6. Crystal structures of [CuL1(py)]ClO4, CuL4, and CuL5 were obtained. These new complexes as well as a series of related symmetrical ones (i.e. CuL7–12) were tested for their in vitro anticancer activity against human liver cancer cell line (Hep-G2) by MTT and apoptosis assay. All of the complexes showed considerable cytotoxic activity against tumor cell lines (IC50 = 5.13–16.24 μg mL−1). The symmetrical CuL7 was the most potent anticancer derivative (IC50 = 5.13 μg mL−1) compared to the control drug 5-FU (IC50 = 5.4 μg mL-1, p < 0.05). Flow cytometry experiments showed that the copper derivatives especially [CuL2(py)]ClO4 and CuL7 induced more apoptosis on Hep-G2 tumor cell lines compared to 5-FU.

[1]  M. Salehi,et al.  Nickel versus copper: enhanced antibacterial activity in a series of new nickel(II) Schiff base complexes , 2016 .

[2]  M. Amirnasr,et al.  Ni(II) and Cu(II) complexes of new unsymmetrical N2O2 Schiff bases derived from 3-(2-aminobenzylimino)-1-phenylbutan-1-ol: synthesis, structure, antibacterial properties, and electrochemistry , 2015 .

[3]  O. Mohammad,et al.  Pharmacologically significant complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) of novel Schiff base ligand, (E)-N-(furan-2-yl methylene) quinolin-8-amine: Synthesis, spectral, XRD, SEM, antimicrobial, antioxidant and in vitro cytotoxic studies , 2015 .

[4]  B. S. Saraswat,et al.  Design, spectral characterization, thermal, DFT studies and anticancer cell line activities of Co(II), Ni(II) and Cu(II) complexes of Schiff bases derived from 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol. , 2015, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[5]  H. A. Rudbari,et al.  Crystal structures, spectroscopic, electrochemical, and antibacterial properties of a series of new copper(II) Schiff base complexes , 2015 .

[6]  C. J. Dhanaraj,et al.  Spectral, thermal, electrochemical, biological and DFT studies on nanocrystalline Co(II), Ni(II), Cu(II) and Zn(II) complexes with a tridentate ONO donor Schiff base ligand , 2015 .

[7]  F. Q. Zhang,et al.  DNA cleavage activities of two dinuclear copper coordination polymers , 2015 .

[8]  B. Mehravi,et al.  New salen-type manganese(III) Schiff base complexes derived from meso-1,2-diphenyl-1,2-ethylenediamine: In vitro anticancer activity, mechanism of action, and molecular docking studies , 2015 .

[9]  Di Xue,et al.  Synthesis, structure, urease inhibitory, and cytotoxic activities of two complexes with protocatechuic acid derivative and phenanthroline , 2015 .

[10]  M. A. Neelakantan,et al.  Mixed ligand Cu(II) complexes containing o-vanillin-l-tryptophan Schiff base and heterocyclic nitrogen bases: synthesis, structural characterization, and biological properties , 2015 .

[11]  Xin Liu,et al.  Self-activated DNA cleavage of a water-soluble mononuclear Cu(II) complex with polyquinolinyl ligand , 2014 .

[12]  P. Li,et al.  Effect of structure and composition of nickel(II) complexes with salicylidene Schiff base ligands on their DNA/protein interaction and cytotoxicity. , 2014, Journal of inorganic biochemistry.

[13]  Jin’an Zhao,et al.  Cytotoxicity towards human alimentary system carcinoma cells resulting from diverse copper(II) complexes , 2014 .

[14]  L. Lindoy,et al.  Mono- and dinucleating Ni(II), Cu(II), Zn(II) and Fe(III) complexes of symmetric and unsymmetric Schiff bases incorporating salicylimine functions - Synthetic and structural studies , 2014 .

[15]  H. A. Rudbari,et al.  Mononuclear and dinuclear salen type copper(II) Schiff base complexes: Synthesis, characterization, crystal structures and catalytic epoxidation of cyclooctene , 2014 .

[16]  Li Tang,et al.  Diorganotin(IV) derivatives of substituted N-hydroxybenzamides with selective cytotoxicity in vitro and potent antitumor activity in vivo. , 2014, Journal of inorganic biochemistry.

[17]  Uma Vuruputuri,et al.  Cellular uptake, cytotoxicity, apoptosis, DNA-binding, photocleavage and molecular docking studies of ruthenium(II) polypyridyl complexes. , 2014, Journal of photochemistry and photobiology. B, Biology.

[18]  Pranaya V. Joshi,et al.  Monitoring cellular uptake and cytotoxicity of copper(II) complex using a fluorescent anthracene thiosemicarbazone ligand. , 2014, Bioconjugate chemistry.

[19]  V. Gandin,et al.  Advances in copper complexes as anticancer agents. , 2014, Chemical reviews.

[20]  M. M. Al-Mogren,et al.  Synthesis, spectroscopic, molecular orbital calculation, cytotoxic, molecular docking of DNA binding and DNA cleavage studies of transition metal complexes with N-benzylidene-N'-salicylidene-1,1-diaminopropane. , 2013, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[21]  Khosro Mohammadi,et al.  Nickel(II) complexes of the unsymmetrical tetradentate Schiff base of methyl-2-(N-2′-aminoethane), (1-methyl-2′-aminoethane), (3-aminopropylamino)cyclopentenedithiocarboxylate: Synthesis, characterization, thermodynamic and computational studies , 2013 .

[22]  V. Kojić,et al.  Antitumor effects of a tetradentate amido-carboxylate ligands and corresponding square-planar palladium(II) complexes toward some cancer cells. Crystal structure, DFT modeling and ligand to DNA probe docking simulation. , 2013, Journal of inorganic biochemistry.

[23]  R. Ammar,et al.  Synthesis, spectroscopic characterization, potentiometric studies, cytotoxic studies and molecular docking studies of DNA binding of transition metal complexes with 1,1-diaminopropane-Schiff base , 2013 .

[24]  R. Karvembu,et al.  Synthesis of triethylphosphite complexes of nickel(II) and palladium(II) with tridentate Schiff base ligand for catalytic application in carbon–carbon coupling reactions , 2012 .

[25]  B. Ko,et al.  Syntheses, structures and DNA cleavage activity of NNO-tridentate Schiff base copper complexes , 2012 .

[26]  Y. Wang,et al.  Synthesis, crystal structure, DNA-binding properties, cytotoxic and antioxidation activities of several ternary copper(II) complexes with a new reduced Schiff base ligand , 2012 .

[27]  L. Zang,et al.  Synthesis and characterization of unsymmetrical oxidovanadium complexes: DNA-binding, cleavage studies and antitumor activities. , 2012, Journal of inorganic biochemistry.

[28]  Lode Vereeck,et al.  Future of nanomedicine: obstacles and remedies. , 2011, Nanomedicine.

[29]  Z. Chohan,et al.  Some new biologically active metal-based sulfonamide. , 2010, European journal of medicinal chemistry.

[30]  M. Patel,et al.  Square pyramidal copper(II) complexes with forth generation fluoroquinolone and neutral bidentate ligand: structure, antibacterial, SOD mimic and DNA-interaction studies. , 2010, Bioorganic & medicinal chemistry.

[31]  S. Keller.  Polyhedron , 2020, Encyclopedia of Database Systems.

[32]  B. N. Sarkar,et al.  Synthesis, molecular and crystalline architectures, and properties of mononuclear cobalt(II)thiocyanates containing a symmetrical tailored diimine/an unsymmetrical bidentate Schiff base , 2009 .

[33]  H. Fun,et al.  Synthesis, characterization and thermodynamic study of copper(II) complexes with unsymmetric tetradentate Schiff base ligands and X-ray structure of {methyl-2-[N-[2-(5-chloro-2-phenolate)methylidynenitrilo]ethyl}aminato(-1)-1-cyclopentenedithiocarboxylatecopper(II) , 2009 .

[34]  S. Mitra,et al.  Synthesis, crystal structures and magnetic behaviors of two dicyanamide bridged di- and polynuclear complexes of cobalt(II) derived from 2,4,6-tris(2-pyridyl)1,3,5-triazine and imidazole , 2009 .

[35]  A. Forni,et al.  Copper(II) Complexes of Tridentate Schiff Bases of 5-Substituted Salicylaldehydes and Diamines - The Role of the Substituent and the Diamine in the Formation of Mono-, Di- and Trinuclear Species - Crystal Structures and Magnetic Properties , 2008 .

[36]  M. Ciriolo,et al.  Double-strand DNA cleavage induced by oxindole-Schiff base copper(II) complexes with potential antitumor activity. , 2008, Journal of inorganic biochemistry.

[37]  D. Oupický,et al.  Synthesis and characterization of new copper thiosemicarbazone complexes with an ONNS quadridentate system: cell growth inhibition, S-phase cell cycle arrest and proapoptotic activities on cisplatin-resistant neuroblastoma cells , 2007, JBIC Journal of Biological Inorganic Chemistry.

[38]  K. Ambroziak,et al.  A synthesis of unsymmetrical chiral salen ligands derived from 2-hydroxynaphthaldehyde and substituted salicylaldehydes , 2007 .

[39]  A. Roth,et al.  Kit for unsymmetric dinucleating double-Schiff-base ligands: facile access to a versatile new ligand system and its first heterobimetallic copper-zinc complex. , 2007, Inorganic chemistry.

[40]  Xinxin Zhao,et al.  Synthesis, crystal structures and cytotoxicities of some transition metal complexes with N-[2-{(pyridin-2-ylmethylidene)amino}ethyl]acetamide. , 2007, Journal of inorganic biochemistry.

[41]  A. Forni,et al.  Copper(II) complexes of salen analogues with two differently substituted (push-pull) salicylaldehyde moieties. A study on the modulation of electronic asymmetry and nonlinear optical properties. , 2006, Inorganic chemistry.

[42]  Q Ping Dou,et al.  Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. , 2006, Cancer research.

[43]  A. Harris,et al.  The Role of Copper in Tumour Angiogenesis , 2005, Journal of Mammary Gland Biology and Neoplasia.

[44]  D. Kyriakidis,et al.  The unexpected formation of biologically active Cu(II) Schiff mono-base complexes with 2-thiophene-carboxaldehyde and dipropylenetriamine: crystal and molecular structure of CudptaSCl2. , 2005, Journal of inorganic biochemistry.

[45]  Daniel F. Brayton,et al.  Disulfiram facilitates intracellular Cu uptake and induces apoptosis in human melanoma cells. , 2004, Journal of medicinal chemistry.

[46]  D. M. Boghaei,et al.  Non-symmetrical tetradentate vanadyl Schiff base complexes derived from 1,2-phenylene diamine and 1,3-naphthalene diamine as catalysts for the oxidation of cyclohexene , 2002 .

[47]  M. Linder.  Biochemistry of Copper , 1991, Biochemistry of the Elements.

[48]  R. Palmer,et al.  Characterization and quantification of copper sulfate-induced vascularization of the rabbit cornea. , 1988, The American journal of pathology.

[49]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[50]  R. Parkins,et al.  A simple preparation of meso-stilbenediamine , 1965 .