Di- and tri-organotin(IV) complexes of arylhydrazones of methylene active compounds and their antiproliferative activity

Abstract Two organotin(IV) complexes, [Sn(C6H5)3HL1] (1) and [Sn(C2H5)2(1κO,2κO-H3L2)(1κO2-H3L2)(μ3-O)]2 (2), were isolated upon interaction of Ph3SnCl and Et2SnO with 2-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)benzoic acid (H2L1) and 2-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene) hydrazinyl)benzoic acid (H4L2), respectively, in toluene solution. Complexes 1 and 2 were characterized by IR and NMR spectroscopies, elemental and single crystal X-ray diffraction analyses. While in 1 the (HL1)– ligand binds the metal in a chelating bidentate mode, in 2 the (H3L2)– anion acts not only as a chelating bidentate but also as a bridging bidentate donor. The in vitro antiproliferative activity against human colorectal carcinoma (HCT116) and human hepatocellular carcinoma (HEPG2) cells lines demonstrated that compound 1 possesses high in vitro antiproliferative activity with IC50 values of 0.0284 ± 0.0001 μM and 0.287 ± 0.0001 μM for HCT116 and HEPG2 cells, respectively.

[1]  M. Biesemans,,et al.  Synthesis, characterization and in vitro antitumor activity of di- and triorganotin derivatives of polyoxa- and biologically relevant carboxylic acids. , 2000, Journal of inorganic biochemistry.

[2]  Qingshan Li,et al.  Redox-active cytotoxic diorganotin(IV) cycloalkylhydroxamate complexes with different ring sizes: reduction behaviour and theoretical interpretation. , 2012, Journal of inorganic biochemistry.

[3]  L. Kabasakal,et al.  Synthesis of Some Novel Azo Derivatives of 3,5‐Dimethly‐1‐(2‐hydroxyethyl)pyrazole as Potent Analgesic Agents , 2006, Archiv der Pharmazie.

[4]  Li Qingshan,et al.  Diorganotin(IV) derivatives of arylhydroxamic acids: synthesis, properties and antitumor activity , 2004 .

[5]  A. R. Fernandes,et al.  Biological characterization of the antiproliferative potential of Co(II) and Sn(IV) coordination compounds in human cancer cell lines: a comparative proteomic approach , 2013, Drug metabolism and drug interactions.

[6]  M. Gielen.  Review: Organotin compounds and their therapeutic potential: a report from the Organometallic Chemistry Department of the Free University of Brussels , 2002 .

[7]  A. Pombeiro,et al.  Copper(II) complexes of arylhydrazones of β-diketones immobilized on Zn–Al layered double hydroxides as effective recyclable catalysts for peroxidative oxidation of alkanes , 2012 .

[8]  A. Pombeiro,et al.  Coordination chemistry of arylhydrazones of methylene active compounds , 2013 .

[9]  M. Singh,et al.  SYNTHESIS AND CHARACTERIZATION OF FOUR- AND FIVECOORDINATE TIN(IV) SALOPHENATES , 1999 .

[10]  L. Pellerito,et al.  Synthesis, structural investigations on organotin(IV) chlorin-e6 complexes, their effect on sea urchin embryonic development and induced apoptosis. , 2005, Journal of inorganic biochemistry.

[11]  M. Xanthopoulou,et al.  Biological studies of organotin(IV) complexes with 2-mercaptopyrimidine , 2007 .

[12]  S. Mukherjee,et al.  Water-Soluble Copper(II) Complexes with a Sulfonic-Functionalized Arylhydrazone of β-Diketone and Their Application in Peroxidative Allylic Oxidation of Cyclohexene , 2012 .

[13]  Qingshan Li,et al.  Cyclic Trinuclear Diorganotin(IV) Complexes – The First Tin Compounds Bearing Oximehydroxamate Ligands: Synthesis, Structural Characterization and High In Vitro Cytotoxicity , 2009 .

[14]  L. Martins,et al.  Trends in properties of para‐substituted 3‐(phenylhydrazo)pentane‐2,4‐diones , 2011 .

[15]  F. M. Chyragov,et al.  Quantum-chemical calculations of the tautomeric forms of 3-phenylazopentane-2,4-dione and the thermodynamic parameters of complexation between its isomers and some metals in aqueous ethanol , 2006 .

[16]  Qingshan Li,et al.  Syntheses, molecular structures, electrochemical behavior, theoretical study, and antitumor activities of organotin(IV) complexes containing 1-(4-chlorophenyl)-1-cyclopentanecarboxylato ligands. , 2011, Inorganic chemistry.

[17]  Qingshan Li,et al.  Synthesis and crystal structure of a mixed-ligand compound di- n -butyl(4-chlorobenzoxy)(4-chlorobenzohydroxamato)tin(IV) , 2005 .

[18]  Qingshan Li,et al.  Polynuclear diorganotin(IV) complexes with arylhydroxamates: Syntheses, structures and in vitro cytotoxic activities. , 2008, Journal of inorganic biochemistry.

[19]  Tautomeric equilibria of para-bromophenyl substituted arylhydrazones of β-diketones , 2011 .

[20]  A. R. Fernandes,et al.  Cobalt complexes bearing scorpionate ligands: synthesis, characterization, cytotoxicity and DNA cleavage. , 2012, Dalton transactions.

[21]  Y. Gho,et al.  Synthetic curcumin analogs inhibit activator protein-1 transcription and tumor-induced angiogenesis. , 2004, Biochemical and biophysical research communications.

[22]  A. Pombeiro,et al.  (E)-2-(2-(2-hydroxyphenyl)hydrazono)-1-phenylbutane-1,3-dione: Tautomery and coordination to copper(II) , 2011 .

[23]  S. Pang,et al.  Anticancer activity of a series of platinum complexes integrating demethylcantharidin with isomers of 1,2-diaminocyclohexane. , 2006, Bioorganic & medicinal chemistry letters.

[24]  Saqib Ali,et al.  Synthesis, Characterization and Crystal Structure of Tetrabutylbis(4,5-dimethoxy-2-nitro benzoato)Distannoxane Dimer , 2011 .

[25]  C. Pettinari,et al.  Chemical and Biotechnological Developments in Organotin Cancer Chemotherapy , 2006 .

[26]  F. Huber,et al.  Organotin compounds and cancer chemotherapy , 1989 .

[27]  Rasim Batmaz,et al.  3-(para-Substituted phenylhydrazo)pentane-2,4-diones: Physicochemical and solvatochromic properties , 2011 .

[28]  Jie Liu,et al.  Syntheses and crystal structures of mononuclear, tetranuclear and hexanuclear organotin compounds with derivatives of p -aminobenzoic acid , 2008 .

[29]  A. Pombeiro,et al.  Template syntheses of copper(II) complexes from arylhydrazones of malononitrile and their catalytic activity towards alcohol oxidations and the nitroaldol reaction: hydrogen bond-assisted ligand liberation and E/Z isomerisation. , 2013, Chemistry.

[30]  J. Bojarşki,et al.  Recent Progress in Barbituric Acid Chemistry , 1985 .

[31]  G. Gilli,et al.  The Nature of the Hydrogen Bond , 2009 .

[32]  A. Kirillov,et al.  Heterometallic Copper(II)–Potassium 3D Coordination Polymers Driven by Multifunctionalized Azo Derivatives of β-Diketones , 2011 .

[33]  D. Cremer,et al.  General definition of ring puckering coordinates , 1975 .

[34]  G. Sheldrick.  A short history of SHELX. , 2008, Acta crystallographica. Section A, Foundations of crystallography.

[35]  Sanjeev Das,et al.  p73β-expressing recombinant adenovirus: a potential anticancer agent , 2005, Cancer Gene Therapy.

[36]  Wanli Kang,et al.  Synthesis, crystal structure and biological activities of four novel tetranuclear di-organotin(IV) carboxylates , 2009 .

[37]  A. Kirillov,et al.  Unusual shift of a nitro group in a phenylhydrazo-β-diketone. , 2011, Dalton transactions.

[38]  J. Ruiz,et al.  Reactions of the polynuclear chain complex [Cu(L)(H2O)]n (H2L is 5-[(2′-carboxyphenyl)azo]-1,3-dimethylbarbituric acid) with imidazole. Crystal structures of the dinuclear and mononuclear derivatives and EPR study of the dimer-monomer equilibrium in solution , 1994 .

[39]  Graham L. Patrick,et al.  An Introduction to Medicinal Chemistry , 1995 .

[40]  Y. Burgart,et al.  Synthesis, analgesic and antipyretic activity of 2-(antipyrin-4-yl)hydrazones of 1,2,3-triketones and their derivatives , 2006, Pharmaceutical Chemistry Journal.

[42]  M. Holčapek,et al.  Synthesis, crystal structures, cytotoxicity and qualitative structure-activity relationship (QSAR) of cis-bis{5-[(E)-2-(aryl)-1-diazenyl]quinolinolato}di-n-butyltin(IV) complexes, (n)Bu2Sn(L)2. , 2008, Journal of inorganic biochemistry.

[43]  L. Pellerito,et al.  Organotin(IV)n+ complexes formed with biologically active ligands: equilibrium and structural studies, and some biological aspects , 2002 .

[44]  G. Stoter,et al.  In vivo toxicological effects and spectral studies of new triorganotin(IV)-N-maleoyltranexamates , 2006 .

[45]  W. Seinen,et al.  Di-n-butyltindichloride uncouples oxidative phosphorylation in rat liver mitochondria. , 1983, Toxicology and applied pharmacology.

[46]  Louis J. Farrugia,et al.  WinGX suite for small-molecule single-crystal crystallography , 1999 .

[47]  Qingshan Li,et al.  New coordination modes of substituted benzohydroxamic acid with dialkyltin(IV) : Structural diversity through ligand isomerization , 2006 .

[48]  Antonio García,et al.  5(2′Carboxy)phenylazo barbiturate diaqua copper(II) trihydrate: Characterization and crystal structure , 1993 .

[49]  O. Yli-Harja,et al.  Synthesis, characterization and antimicrobial activity of arylhydrazones of methylene active compounds , 2012, Pharmaceutical Chemistry Journal.

[50]  A. Pombeiro,et al.  Ortho-hydroxyphenylhydrazo-β-diketones: tautomery, coordination ability, and catalytic activity of their copper(II) complexes toward oxidation of cyclohexane and benzylic alcohols. , 2011, Inorganic chemistry.

[51]  J. Ruiz,et al.  Preparation, crystal structures and magnetic properties of a syn-anti carboxylate-bridged dinuclear copper(II) complex and its precursor, a hydrogen-bonded polynuclear copper(II) complex , 1994 .

[52]  O. Chupakhin,et al.  2-(Het)arylhydrazono-1,3-dicarbonyl compounds in organic synthesis , 2010 .

[53]  A. Pombeiro,et al.  1D Cu(II) coordination polymer derived from 2-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)benzenesulfonate chelator and pyrazine spacer , 2013 .

[54]  Z. Ciunik,et al.  Organotin mefenamic complexes—preparations, spectroscopic studies and crystal structure of a triphenyltin ester of mefenamic acid: novel anti‐tuberculosis agents , 2002 .

[55]  A. Pombeiro,et al.  Water‐Soluble Cobalt(II) and Copper(II) Complexes of 3‐(5‐Chloro‐2‐hydroxy‐3‐sulfophenylhydrazo)pentane‐2,4‐dione as Building Blocks for 3D Supramolecular Networks and Catalysts for TEMPO‐Mediated Aerobic Oxidation of Benzylic Alcohols , 2011 .

[56]  F. M. Chyragov,et al.  Photometric determination of copper(II) in nickel alloys using azoderivatives of ethyl acetoacetate , 2008 .

[57]  P. Kapoor,et al.  SOLUTION AND SOLID STATE MOLECULAR STRUCTURES OF DIALKYLTIN(IV) β-NAPHTHOATES : [R2Sn(OCOC10H7)}2O]2, R2Sn(OCOC10H7)2 AND (CH3)4N+[R2Sn(OCOC10H7)3]- (R= n-C4H9 and CH3). X-RAY CRYSTAL STRUCTURES OF [{n-C4H9)2Sn(OCOC10H7)}2O]2 AND [(n-C4H9)2Sn(OCOC10H7)2] , 2002 .

[58]  Rayees U. H. Mattoo,et al.  Synthesis, Characterization and Antimicrobial Activity of Long-Chain Hydrazones , 2008 .

[59]  L. Ballarin,et al.  TBT-induced apoptosis in tunicate haemocytes , 1999 .

[60]  F. Pashaev,et al.  Complexation of copper(II) with 3-(2-hydroxyphenylazo)pentadione-2,4 , 2006 .

[61]  Saqib Ali,et al.  Organotin(IV) 4-methoxyphenylethanoates: Synthesis, spectroscopic characterization, X-ray structures and in vitro anticancer activity against human prostate cell lines (PC-3) , 2009 .

[62]  L. Martins,et al.  Synthesis, structure and electrochemical behaviour of Na, MgII, MnII, ZnII, CdII and NiII complexes of 3-(2-carboxyphenylhydrazone)pentane-2,4-dione , 2013 .

[63]  M. Holčapek,et al.  Synthesis, characterization, cytotoxic activity and crystal structures of tri- and di-organotin(IV) complexes constructed from the β-{[(E)-1-(2-hydroxyaryl)alkylidene]amino}propionate and β-{[(2Z)-(3-hydroxy-1-methyl-2-butenylidene)]amino}propionate skeletons , 2006 .

[64]  H. Yin,et al.  Di- and tri-organotin(IV) complexes with 2-hydroxy-1-naphthaldehyde 5-chloro-2-hydroxybenzoylhydrazone: Synthesis, characterization and in vitro antitumor activities , 2013 .

[65]  Ş. Küçükgüzel,et al.  Synthesis and antimycobacterial activity of some coupling products from 4-aminobenzoic acid hydrazones , 1999 .

[66]  Muhammad Ashfaq.  Synthesis of novel bioactive phthalimido-4-methyl pentanoateorganotin(IV) esters with spectroscopic investigation , 2006 .

[67]  E. Hey‐Hawkins,et al.  Study of the cytotoxic activity of di and triphenyltin(IV) carboxylate complexes. , 2008, Journal of inorganic biochemistry.

[68]  B. Gil-Hernández,et al.  Copper(II) complexes with a new carboxylic-functionalized arylhydrazone of β-diketone as effective catalysts for acid-free oxidations , 2012 .

[69]  Gastone Gilli,et al.  The Nature of the Hydrogen Bond: Outline of a Comprehensive Hydrogen Bond Theory , 2009 .

[70]  Qingshan Li,et al.  Mononuclear diorganotin(IV) complexes with arylhydroxamates: syntheses, structures and assessment of in vitro cytotoxicity , 2007 .

[71]  Qingshan Li,et al.  Diorganotin(IV) derivatives of substituted benzohydroxamic acids with high antitumor activity. , 2004, Chemistry.

[72]  L. Martins,et al.  Complexes of copper(II) with 3-(ortho-substituted phenylhydrazo)pentane-2,4-diones: syntheses, properties and catalytic activity for cyclohexane oxidation. , 2011, Dalton transactions.

[73]  M. Gielen.  An overview of forty years organotin chemistry developed at the Free Universities of Brussels ULB and VUB , 2003 .

[74]  J. Ruiz,et al.  Structural and magnetic studies of a syn-anti carboxylate-bridged helix-like chain copper(II) complex , 1992 .

[75]  M. I. Khan,et al.  Biological aspects of new organotin(IV) compounds of 3-maleimidopropionic acid , 2004 .

[76]  Wanli Kang,et al.  Synthesis, crystal structure and biological activities of two novel organotin(IV) complexes constructed from 12-(4-methylbenzoyl)-9,10-dihydro-9,l0-ethanoanthracene-11-carboxylic acid , 2009 .

[77]  Anant B. Patel,et al.  Synthesis, spectroscopic, electrochemical and antibacterial studies of new Ru(II) 1,10-phenanthroline complexes containing aryldiazopentane-2,4-dione as co-ligand , 2000 .

[78]  C. Boone,et al.  How curcumin works preferentially with water soluble antioxidants. , 2001, Journal of the American Chemical Society.

[79]  E. Ashry,et al.  Synthesis of antipyrine derivatives derived from dimedone , 2007 .

[80]  F. Uckun,et al.  X-ray structure, solution properties, and biological activity profile of vanadocene(IV) acetylacetonate complex, [VCp2(acac)](CF3SO3): a dual-function anti-cancer agent with anti-angiogenic and anti-mitotic properties , 2001 .

[81]  C. Pettinari,et al.  Water-soluble heterometallic copper(II)-sodium complex comprising arylhydrazone of barbituric acid as a ligand , 2012 .

[82]  P. Novák,et al.  Structure of azo dye organotin(IV) compounds containing a C, N-chelating ligand, part II, and their in vitro antifungal activity , 2005 .

[83]  H. Yin,et al.  Synthesis and spectroscopic properties of [N-(4-carboxyphenyl) salicylideneiminato] di- and tri-organotin (IV) complexes and crystal structures of {[nBu2Sn(2-OHC6H4CHNC6H4COO)]2O}2 and Ph3Sn(2-OHC6H4CHNC6H4COO) , 2005 .