Synthesis,characterization, and cytotoxicity of platinum(II)/palladium(II) complexes with 4-toluenesulfonyl-L-amino acid dianion and diimine/diamine

Eight new platinum(II)/palladium(II) complexes with 4-toluenesulfonyl-L-amino acid dianion and diimine/diamine ligands, [Pd(en)(Tsile)]·H₂O (1), [Pd(bipy)(Tsile)] (2), [Pd(bipy)(Tsthr)]·0.5H₂O (3), [Pd(phen)(Tsile)]·0.5H₂O (4), [Pd(phen)(Tsthr)]·H₂O (5), [Pd(bqu)(Tsthr)]·1.5H₂O (6), [Pt(en)(Tsser)] (7), and [Pt(en)(Tsphe)]·H₂O (8), have been synthesized and characterized by elemental analyses, ¹H NMR and mass spectrometry. The crystal structure of 7 has been determined by X-ray diffraction. Cytotoxicities were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamine B assays. The complexes exert cytotoxicity against HL-60, Bel-7402, BGC-823, and KB cell lines with 4 having the best cytotoxicity against HL-60, Bel-7402, and BGC-823 cell lines; the compounds are less cytotoxic than cisplatin.     

Synthesis,characterization and cytotoxicity of gold(III) complexes with deprotonated pyridyl carboxamide

Six new gold(III) complexes [Au(bzpam)Cl₂] (1, bzpamH = N‐benzyl picolinamide), [Au(hetpam)Cl₂] (2, hetpamH = N‐(2‐hydroxyethyl) picolinamide), [Au(pypam)Cl]AuCl₄ (3, pypamH = N‐(pyridin‐2‐ylmethyl) picolinamide), [Au(dmepam)Cl]AuCl₄ (4, dmepamH = N‐(2‐(dimethylamino)ethyl) picolinamide), [Au(bhetpydam)Cl] (5, bhetpydamH₂ = N,N′‐bis(2‐hydroxyethyl) pyridine‐ 2,6‐dicarboxamide) and [Au₂(hedam)Cl₄] (6, hedamH₂ = N,N′‐(hexane‐1,6‐diyl) dipicolinamide) with deprotonated pyridyl carboxamide were synthesized and characterized by elemental analysis, molar conductivity, IR, H¹ NMR and C¹³ NMR techniques. The analytical data showed that deprotonated pyridyl carboxamide coordinated with gold(III) ions through a nitrogen atom. The cytotoxicity against Bel‐7402 and HL‐60 cell lines was tested by MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) and SRB (sulforhodamine B) assays. The results indicated that the complexes exerted cytotoxic effects against Bel‐7402 and HL‐60 cell lines, complex 6 had better cytotoxicity than cisplatin, and complex 3 displayed similar cytotoxicity to cisplatin against Bel‐7402 cell line. The results suggested that the characteristics of ligands had an important effect on cytotoxicity of complexes. Copyright © 2012 John Wiley & Sons, Ltd.     

Non‐Flat Bisbenzylisoquinoline Alkaloid Fangchinoline As a Class of Potent G‐Quadruplex Stabilizer with Anti‐cancer Activity

Compounds selectively binding and stabilizing G‐quadruplex structures could inhibit the telomerase or down‐ regulate the oncogenes and may act as anti‐cancer drugs. An alkaloid with non‐flat structure, fangchinoline, showed to strongly stabilize the intermolecular and intramolecular parallel stranded G‐quadruplex structure, increasing melting temperature by 20 and 23°C, respectively. The binding mode was investigated by using NMR and molecular modelling methods. Four human cell lines (HL‐60, BGC‐823, Bel‐7402 and KB) were taken to test the anti‐proliferation effects of fangchinoline and the IC₅₀ values were ranged from 16 to 32 µmol/L. These results showed that the fangchinoline or related moiety derivatives may represent a class of telomere‐targeted agents as potential anti‐cancer drugs.     

Platinum(II) complexes of reduced amino acid ester Schiff bases: synthesis, characterization, and antitumor activity

A series of platinum(II) complexes of reduced amino acid esters Schiff bases were synthesized as potential anticancer agents and characterized by ¹H NMR, EA, IR, and molar conductivity. These compounds were tested for their DNA interaction with salmon sperm DNA by ultraviolet spectrum and CD spectrum, and their in vitro anticancer activities have been validated against HL-60, KB, BGC-823, and Bel-7402 cell lines by MTT assay. The cytotoxicity of complexes 5d and 5f are better than cisplatin against Bel-7402 cell lines, and show a close cytotoxic effect against HL-60 cell line.     

Synthesis,characterization, and cytotoxicity of complexes of platinum(II) with 2,2′-bipyridine and N-benzoyl-L-amino acid dianion

Four new platinum(II) complexes (1–4) with N-benzoyl-L-amino acid and bipy were synthesized and characterized by elemental analysis, IR, UV, ¹H NMR, and mass spectra. The crystal structure of 1 was determined by X-ray diffraction analysis. Cytotoxicities were measured by MTT and SRB assays. Complexes 1–4 exert cytotoxicity with selectivity against HL-60, Bel-7402, BGC-823, and KB cell lines. This suggests that amino acids and acylated groups have important effects on cytotoxicity; the cytotoxicity is also related to the species of tumor cells, but the IC₅₀ values do not show definite correlation with the variation of amino acids and acylated groups.     

Copper(II), palladium(II) and platinum(II) chloride complexes with 5-amino-2-tert-butyltetrazole: Synthesis, characterization and cytotoxicity

Complexes CuL₃Cl₂, PdL₂Cl₂ and PtL₂Cl₂, where L is a novel ligand from the series of 2-substituted 5-aminotetrazoles, namely 5-amino-2-tert-butyltetrazole (1), have been synthesized by the reaction of metal(II) chlorides with 1 and characterized by IR spectroscopy, thermal and X-ray analyses. The crystallographic structural analysis of these complexes revealed that 1 acts as a monodentate ligand coordinated to the metal via endocyclic N4 atom. Platinum complex demonstrates promising cytotoxicity against human cervical carcinoma cells with IC₅₀ value average between those of cisplatin and carboplatin.     

Synthesis,antitumor activity and crystal structure of the triphenyltin derivative of exo‐7‐oxa‐bicyclo[2,2,1]hept‐5‐ene‐3‐N‐p‐tolylamide‐2‐acid

The synthesis and crystal structure of­Ph₃SnO₂CCHCHCH:CHCH(O)CHCONHC₆H₄­CH₃·CH₂Cl₂ are reported. The monomer units­are bridged by the carbonyl oxygen of the amide group, thus forming a polymer in which each tin atom is best described as having a distorted five‐coordinate geometry. There is a relatively strong intramolecular hydrogen bond between the amide hydrogen and the ether oxygen. The in vitro antitumor activities of the title compound against HL‐60, BGC‐823, Bel‐7402, SKOV3, KB and Hela tumor lines are reported. The title compound shows a distinct advantage when the metal (tin) is introduced into the acid.Copyright © 2001 John Wiley & Sons, Ltd.     

Synthesis,characterization, and anticancer activity of some azole‐heterocyclic complexes with gold(III), palladium(II), nickel(II), and copper(II) metal ions

Four new complexes of Au(III), Pd(II), Ni(II), and Cu(II) ions were synthesized, derived from a novel heterocyclic ligand (L) that has both triazole and tetrazole rings. The ligand synthesis was through successive steps to achieve both heterocyclic rings. The synthesized compounds were characterized using conventional techniques like infrared, ultra violet—visible and proton/carbon nuclear magnetic resonance spectroscopy, metal and thermal analyses, and molar conductivity. All complexes were suggested to have square planar geometry, gold, nickel, and palladium complexes were salts while copper neutral complexes have the chemical formulas; [AuL₂]Cl.2H₂O, [PdL₂]Cl₂.2H₂O, [NiL₂]Cl₂.2H₂O, and [CuL₂]. The cytotoxic effect was studied on breast cancer cell line (MCF‐7 cell line) at different concentrations by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay method, for the ligand (L) and complexes. The results showed that gold(III) and nickel(II) complexes have the highest cytotoxicity among all compounds against cancer cell lines.     

Synthesis,structure and in vitro cytotoxicity of platinum(II) complexes containing eugenol and a quinolin‐8‐ol‐derived chelator

The synthesis of potassium (η²‐4‐allyl‐2‐methoxyphenol)trichloridoplatinate(II), K[PtCl₃(C₁₀H₁₂O₂)], ( 1 ), starting from Zeise's salt and Ocimum sanctum L. oil has been optimized. Starting from ( 1 ), three new platinum(II) complexes, namely (η²‐4‐allyl‐2‐methoxyphenol)chlorido(2‐methylquinolin‐8‐olato‐κ²N ,O )platinum(II), ( 2 ), (η²‐4‐allyl‐2‐methoxyphenol)chlorido(5‐nitroquinolin‐8‐olato‐κ²N ,O )platinum(II), ( 3 ), and (η²‐4‐allyl‐2‐methoxyphenol)chlorido(5,7‐dichloroquinolin‐8‐olato‐κ²N ,O )platinum(II), [Pt(C₉H₄Cl₂NO)Cl(C₁₀H₁₂O₂)], ( 4 ), containing eugenol and a quinolin‐8‐ol derivative (R‐OQ), have been synthesized and characterized by elemental analyses, MS, IR, ¹H NMR and NOESY spectra. For ( 1 ) and ( 4 ), single‐crystal X‐ray diffraction studies were also carried out. Complexes ( 2 )–( 4 ) show good inhibiting abilities on three human cancer cell lines, i.e. KB, Hep‐G2 and LU, with IC₅₀ values of 1.42–17.8 µM . Complex ( 3 ) gives an impressively high activity against KB, Hep‐G2, LU and MCF‐7, with IC₅₀ values of 1.42–4.91 µM , which are much lower than those of cisplatin and some other platinum(II) complexes.     

Synthesis,spectral and antibacterial activity of Co(II), Ni(II) and Zn(II) complexes with 2‐hydroxy‐benzoic acid(3,4‐dihydro‐2H‐naphthalen‐1‐ylidene)‐hydrazide

A bioactive Schiff base HL i.e. 2‐hydroxy‐benzoic acid(3,4‐dihydro‐2H ‐naphthalen‐1‐ylidene)‐hydrazide was synthesized by reacting equimolar amount of salicylic acid hydrazide and 1‐tetralone. Co(II), Ni(II) and Zn(II) complexes of ligand HL was synthesized in 1:1 and 1:2 molar ratio of metal to ligand. The structure of the synthesized ligand and metal complexes was established by elemental analysis, molar conductance, magnetic susceptibility measurements, electronic, IR and EPR spectral techniques. For determining the thermal stability the TGA has been done. In DFT studies the geometries of Schiff bases and metal complexes were fully optimized with respect to the energy using the 6–31 + g(d,p) basis set. Spectral data reveal that ligand behave uninegative tridentate in ML complexes and uninegative bidentate in ML₂ complexes. On the basis of characterization octahedral geometry has been assigned for Co(II) and Ni(II) complexes, while tetrahedral for Zn(II) complexes. Antibacterial activity of the synthesized compounds were evaluated against Staphylococcus aureus , Bacillus subtilis, Escherichia coli , Xanthomonas campestris and Pseudomonas aeruginosa and the results revealed that metal complexes show enhanced activity in comparison to free ligand.     

Co(II), Ni(II), Cu(II) and Zn(II) complexes of aminothiazole‐derived Schiff base ligands: Synthesis,characterization, antibacterial and cytotoxicity evaluation,bovine serum albumin binding and density functional theory studies

Transition metal complexes of type M(L)₂(H₂O)_x were synthesized, where L is deprotonated Schiff base 2,4‐dihalo‐6‐(substituted thiazol‐2‐ylimino)methylphenol derived from the condensation of aminothiazole or its derivatives with 2‐hydroxy‐3‐halobenzaldehyde and M = Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺ (x = 0 for Cu²⁺ and Zn²⁺; x = 2 for Co²⁺ and Ni²⁺). The synthesized Schiff bases and their metal complexes were thoroughly characterized using infrared, ¹H NMR, electronic and electron paramagnetic resonance spectroscopies, elemental analysis, molar conductance and magnetic susceptibility measurements, thermogravimetric analysis and scanning electron microscopy. The results reveal that the bidentate ligands form complexes having octahedral geometry around Co²⁺ and Ni²⁺ metal ions while the geometry around Cu²⁺ and Zn²⁺ metal ions is four‐coordinated. The geometries of newly synthesized Schiff bases and their metal complexes were fully optimized in Gaussian 09 using 6–31 + g(d,p) basis set. Fluorescence quenching data reveal that Zn(II) and Cu(II) complexes bind more strongly to bovine serum albumin in comparison to Co(II) and Ni(II) complexes. The ligands and their complexes were evaluated for in vitro antibacterial activity against Escherichia coli ATCC 25922 (Gram negative) and Staphylococcus aureus ATCC 29213 (Gram positive) and cytotoxicity against lever hepatocellular cell line HepG2.     

Synthesis,characterization, and cytotoxicity of mixed-ligand complexes of palladium(II) with 1,10-phenanthroline and N-carbonyl-L-isoleucine dianion

Three novel palladium(II) complexes [Pd(Phen)(Bzile)] (I), [Pd(Phen)(p-mBzile)] (II), and [Pd(Phen)(p-NBzile)] · H₂O (III), where Bzile = N-benzoyl-L-isolecine), p-MBzile = N-(p-methylbenzoyl)-L-isolecine), p-NBzile = N-(p-nitrobenzoyl)-L-isolecine), have been synthesized and characterized by elemental analysis, ES-MS, and IR. The crystal and molecular structure of the complex II has been determined by single crystal X-ray diffraction. The cytotoxicity was tested against carcinoma cell lines: KB, BGC-823, Bel-7402 and HL-60 by MTT assay. The results indicated that these complexes exerted cytotoxicity, but none of them showed higher cytotoxicity than cisplatin. The cytotoxicity against HL-60, BGC-823, Bel-7402 and KB cell lines decreases in the sequence: p-MBzile > Bzile > p-NBzile. It suggests that the acylated groups have important impact on the cytotoxicity of complexes.     

芳香亚胺与N-(4-甲基苯甲酰)-L-缬氨酸双阴离子合钯(Ⅱ)配合物的合成、晶体结构及体外抗肿瘤活性

本文首次报道了2个钯(Ⅱ)的配合物[Pd(bipy)(4-CH3Bzval-N,O)](1)和[Pd(phen)(4-CH3Bzval-N,O)](2)(bipy=2,2′-联吡啶,phen=1,10-菲咯啉,4-CH3Bzval-N,O=N-(4-甲基苯甲酰)-L-缬氨酸双阴离子)的合成及晶体结构,利用MTT法和SRB法研究了配合物的体外抗肿瘤活性。配合物2属单斜晶系P21/n空间群,其中a=1.162 92(8)nm,b=1.074 03(7)nm,c=1.821 14(12)nm,V=2.232 8(3)nm3,Z=4。结果显示:2个配合物对HL-60,BGC-823,Bel-7402和KB 4种人的肿瘤细胞表现出一定的活性和选择性,但其活性均小于顺铂。     

Mononuclear diorganotin(IV) complexes with arylhydroxamates: syntheses,structures and assessment of in vitro cytotoxicity

Two series of diorganotin(IV) complexes with dihalogenobenzohydroxamate ligands (substituents = 2,4‐Cl₂, 2,4‐F₂, 3,4‐F₂, 2,5‐F₂, 2,6‐F₂), formulated as [R₂Sn(HL)₂] ( a ), and the arylhydroxamato/arylcarboxylato mixed‐ligand complexes [R₂Sn(HL)(L′)] ( b ), were prepared and characterized by FT‐IR, ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopies, elemental analyses and melting point measurements. X‐ray diffraction analysis was also carried out for the complex [Me₂Sn{3,4‐F₂C₆H₃C(O)NHO}₂], 1a . These compounds exhibit in vitro cytotoxic activities towards human leukemic promyelocites HL‐60, BGC‐823, BEL‐7402 and KB cell lines which, in some cases, are identical to, or even higher than, that of cisplatin. The type, position and number of the X substituents in the phenyl ring play a role in the cytotoxic activity, and complex 8a , with its 2,6‐difluorobenzohydroxamato ligand, is highly active against all tumor cells. A tentative structure–activity relationship is also described. Copyright © 2007 John Wiley & Sons, Ltd.     

新型钯配合物[Pd(Phen)(TsserNO)]·H_2O的合成、晶体结构和体外抗肿瘤活性(英文)

A novel palladium(Ⅱ) complex [Pd(Phen)(TsserNO)]·H2O (Phen=1,10-phenanthroline; TsserNO=4- toluenesulfonyl-L-serinate dianion) has been prepared and structurally characterized, the cytotoxicity in vitro has also been investigated by MTT and SRB assays. The complex crystallizes in the monoclinic system, space group P21 with cell parameters a=0.618 64(14) nm, b=1.768 9(4) nm, c=0.990 2(2) nm, β=102.392(4)°, V=1.058 3(4) nm3 and Z=2. The complex had selectivity against HL-60, BGC-823, Bel-7402 and KB cells lines, its cytotoxicity is equal to that of cisplatin against BGC-823 and Bel-7402 cells lines, however it is less potent than cisplatin against HL-60 and KB cell lines.Keywordsantitumor; palladium(Ⅱ) complex; crystal structure     

DNA Binding Studies and Cytotoxicity of Ethylenediamine 8‐Hydroxyquinolinato Palladium(II) Chloride

Interaction between ethylenediamine 8‐hydroxyquinolinato palladium(II) chloride and calf thymus DNA (CT‐DNA) in aqueous solution were studied by UV‐Visible absorption, fluorescence spectroscopic techniques and gel chromatography at temperatures of 300 K and 310 K. The complex bound strongly and intercalatively to the CT‐DNA. The results of the cytotoxicity assay of the Pd(II) complex on the leukemia cell line, K562 indicated lower cytotoxicity than cisplatin. The Pd(II) complex is considered an agent with potential antitumor activity. The calculation of several binding and thermodynamic parameters of the inclusion Pd(II) complex with CT‐DNA may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.     

Complexes of Co(II), Ni(II) and Cu(II) with lapachol

Complexes of naturally occurring hydroxynaphtho-quinone, lapachol (2-hydroxy-3(3-methyl-2-buthenyl)-1,4-naphthoquinone = HL) with Co(II), Ni(II) and Cu(II) have been prepared by reaction of the corresponding acetates with the ligand (HL) in ethanol. The molecular and crystal structures were determined for [CoL₂(EtOH)₂] (1), [NiL₂(EtOH)₂] (2), and [CuL₂(py)₂] (3). In all cases the deprotonated lapachol behaves as chelating bidentate ligand. The complexes were also characterized by elemental analyses, cyclic voltammetry, and FAB-MS.     

Synthesis and in vitro antitumor activity of some tetraphenylantimony derivatives of exo‐7‐oxa‐bicyclo[2,2,1] heptane (ene)‐3‐arylamide‐2‐acid

A series of novel tetraphenylantimony derivatives of exo‐7‐oxa‐bicyclo[2,2,1] heptane (ene)‐3‐arylamide‐2‐acid of the general formula Ph₄SbO₂CCHCHCH₂CH₂CH(O)HCONHAr (Ar = Ph,4‐ClC₆H₄, 4‐BrC₆H₄, 3‐BrC₆H₄, 4‐F‐3‐ClC₆H₃ and 4‐MeC₆H₄) have been synthesized and characterized by elemental analysis, IR, ¹H NMR and mass spectra. The crystal structure of Ph₄SbO₂CCHCHCH₂CH₂CH(O)HCONHC₆­H₄CH₃·CHCl₃ was determined by X‐ray diffraction. Five human neoplastic cell lines (HL‐60, KB, Bel‐7402, BGC‐823 and HCT‐8) were used to screen these compounds. The results indicate that these compounds at 10 µM show certain in vitro antitumor activities. Copyright © 2001 John Wiley & Sons, Ltd.     

Biomolecular docking,antimicrobial and cytotoxic studies on new bidentate schiff base ligand derived metal (II) complexes

Three new metal complexes [Cu(L)₂] (1), [Co(L)₂] (2) and [Zn(L)₂] (3) have been prepared by the reaction of hydrated salts of metal (II) acetate with new Schiff base ligand HL, [2‐((4‐(dimethylamino)phenylimino)methyl)‐4,6‐di‐t‐butylphenol] and characterized by different physico‐chemical analyses such as elemental analysis, single XRD, ¹H NMR, FTIR and UV–Vis spectroscopic techniques. Their biomolecular docking, antimicrobial and cytotoxicity studies have also been demonstrated. The proposed structure of Schiff base ligand HL and complex 2 are confirmed by Single crystal X‐ray crystallography study. This analysis revealed that metal (II) complexes remain in distorted tetrahedral coordination environments. The electronic properties such as HOMO and LUMO energies are carried out by gaseous phase DFT/B3LYP calculations using Gaussian 09 program. Complex 1 showed a good binding propensity to the DNA and HSA, during the assessment of docking studies. Schiff base ligand HL and its metal (II) complexes, 1–3 screened for their in vitro antimicrobial activities using the disc diffusion method against selected microbes. Complex 1 shows higher antimicrobial activity than complexes 2, 3 and Schiff base ligand HL. According to the results obtained from the cytotoxic studies, Schiff base ligand HL and its metal (II) complexes 1–3 have better cytotoxicity against MCF‐7 cell lines with potency higher than the currently used chemotherapeutic agent cyclophosphamide.     

Synthesis,DNA binding,nuclease activity and cytotoxic studies of a wheel‐shaped octanuclear copper(II) complex based on 1,2,4‐triazole

The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds. Among the metal compounds synthesized and tested, copper compounds have received considerable attention because of their cytotoxic activity against solid tumors. A novel wheel‐shaped octanuclear copper(II) complex with a 1,2,4‐triazole derivative ligand formulated as [Cu₈L₄](ClO₄)₈?11H₂O ( 1 ) (L = 3,5‐bis((bis(2‐hydroxylethyl)amino)methyl)‐4 H‐1,2,4,‐triazole‐4‐amine) has been synthesized and structurally characterized. In 1 , eight Cu atoms are linked through 1,2,4‐triazole units and alkoxide bridges to form a centrosymmetric octanuclear Cu(II) metallomacrocycle. The interaction of complex 1 with calf thymus DNA has been studied using UV absorption, fluorescence and circular dichroism spectroscopies, viscosity measurements and cyclic voltammetry. The apparent binding constant (k_app) value for 1 is 1.59 × 10⁵ M^?1. Furthermore, complex 1 displays efficient oxidative cleavage of supercoiled DNA in the presence of external agents, the rate constant for the conversion of supercoiled to nicked DNA being 2.67 × 10^?5 s^?1. Interestingly, cytotoxicity studies on the MCF‐7 human breast cancer cell line show that the IC₅₀ value of 1 is less than that of cisplatin for the same cell line, revealing that it has the potential to act as an effective metal‐based anticancer drug. Copyright © 2016 John Wiley & Sons, Ltd.