Antitumor Activity Of Complexes Research Articles

A 24-membered macrocyclic triorganotin(IV) carboxylate: Synthesis, characterization, crystal structure, and antitumor activity

A novel organotin carboxylate based on an amide carboxylic acid, (Ph3Sn)6(L)6 (complex 1) (L = 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)acetic acid), was designed and synthesized. The complex was characterized using elemental analysis, IR spectroscopy, and 1H, 13C, and 119Sn NMR spectroscopy. X-ray crystallography diffraction analysis revealed that the complex is a hexanuclear triphenyltin carboxylate macrocycle. Each bridging ligand of the macrocycle coordinates with two Sn atoms. Intermolecular π···π interactions link the complex into a complicated supramolecular structure, which is discussed in detail. The fluorescence and antitumor activities of complex 1 were also studied.

Lysosomal‐targeted anticancer half‐sandwich iridium(III) complexes modified with lonidamine amide derivatives

Ten half‐sandwich iridium complexes containing lonidamine amide derivatives were synthesized and characterized. Unlike lonidamine, which acts on mitochondria, its iridium complexes successfully targeted lysosomes and induced lysosomal damage. Antiproliferation studies showed that most of the complexes have higher anticancer activity against A549 and HeLa cells than cisplatin. The antitumor activity of complex 6 is 2.69 times that of cisplatin against A549 cells. We also performed antitumor tests on ligands L1 and L5, and proved that they exhibit excellent antitumor activity only after binding to the metal center. The bovine serum albumin (BSA) binding test showed that the complexes had the ability to bind to BSA, and they interact with BSA by a static mechanism. The complexes can also cause changes in mitochondrial membrane potential and can produce active oxygen species better than active control. NADH/NAD+ transformation experiments were used to determine if the production of ROS was caused by the transformation of NADH/NAD+. We also explored the way that the complexes enter cells.

Synthesis, structural characterization and in vitro anticancer activity of two new nickel complexes bearing imine bonds

Herein, we describe the synthesis and characterization of two novel nickel complexes, [Ni(L1)2] (1) and [Ni(L2)2(CH3COO)]·9H2O(CH3COOH) (2), containing (E)-2-(((2-(diethylamino)ethyl)imino)methyl)-6-ethoxyphenol (HL1) and (E)-2-(((2-(dimethylamino)ethyl)imino)methyl)-6-methoxyphenol (HL2) ligands. Complexes have been synthesized under conventional methods and characterized by elemental analysis, FT-IR, ICP-OES, TGA, and single crystal X-ray diffraction analysis. The geometry of the 2 is also supported by magnetic susceptibility and Q-TOF LC/MS analysis. The nickel ions are in square planar and distorted octahedral coordination environments, respectively. Complex 1 and 2 crystallizes in the monoclinic C1 c1 and C1 2/c1 space group. The antitumor activities of complexes 1–2 have been investigated. Both of the complexes showed dose dependent cytotoxicity and killed the newly established lung cancer cells via apoptotic pathway. The novel nickel complexes were determined as potential antitumor agents.

Synthesis, structures and biological activity of novel complexes with trifluorinated anthranilic acid derivatives

Two cobalt complexes [Co2(L)(phen)(Ac)(PLC)] (1), [Co3(HL)4(CH3O)2(H2O)2] (2) and one zinc complex [Zn2(L)(phen)(Ac)(PLC)] (3), (L = (2-carboxylato-5-(trifluoromethyl)phenyl) (3-hydroxy-4-methoxyphenoxy)amide, phen = 1,10-phenanthroline, Ac = acetate, PLC = 2-amino-4-trifluoromethylbenzoate) have been synthesized and characterized by physicochemical and spectroscopic methods. In addition, X-ray crystallography shows that the Co and Zn atoms in each complex are penta- or six-coordinated, adopting a twisted square pyramid or triangular bi-conical geometry. The antitumor activity of complex against A549 (human lung cancer cells) and Hela (human cervical cancer cells) was screened. Results show that 3 exhibits the most effective antitumor activity (IC50 = 1.369–2.129 μM). Antimicrobial studies also show that 3 exhibits the highest activity.

A novel octa-nuclear 32-membered zirconocene macrocycle based on the aromatic selenite.

A novel macrocyclic zirconocene(iv) aromatic selenite [(CpZr)8L16]·2(Cp4Zr2(μ-O)Cl2) (complex 1) (Cp = cyclopentadienyl anion; L = 4-fluorobenzeneseleninic acid) was prepared by the reaction of bis(cyclopentadienyl)zirconium dichloride with 4-fluorobenzeneseleninic acid and characterized by elemental analysis, infrared spectroscopy, 1H, 13C NMR spectroscopy, ESI-MS, XRD and X-ray diffraction. The structure analysis shows that complex 1 is a centrosymmetric 32-membered macrocycle containing an eight-nuclear zirconocene. In this complex, the 4-fluorobenzeneseleninic acid ligands adopt bidentate mode in coordinating to zirconium, which play a bridging role in the formation of a macrocycle. The title compound is a rare example of aromatic selenic acid-based zirconocene derivatives. Furthermore, the preliminary in vitro anti-tumor activity of complex 1 has also been studied toward breast cancer cell lines (MDA-MB-231) and human cervix cell lines (HeLa). The results indicate that complex 1 shows higher activity compared with the ligand and bis(cyclopentadienyl)zirconium dichloride.

Synthesis, crystal structure and antitumor effect of a novel copper(II) complex bearing zoledronic acid derivative.

A great majority of Cu(II) complexes currently studied in the anticancer research field exert their antiproliferative activities through ligand exchange. In this work, we present the synthesis and structural characterization of two novel Cu(II) complexes, {[Cu3(ZL)2(H2O)6]·6H2O}n (1) (ZL=1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid) and [Cu(IPrDP)2]·3H2O (2) (IPrDP=1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid). Due to the insolubility of polymer 1 in common solvents, only the biological activities of complex 2 were investigated. The antitumor activity of complex 2 was evaluated against a panel of human cancer cell lines, including U2OS, A549, HCT116, MDA-MB-231 and HepG2. Complex 2 exhibited comparable cytotoxic effect to cisplatin (CDDP) against the human colon carcinoma cells HCT116, and superior selectivity for inhibiting human hepatocarcinoma cells rather than normal liver cells. The cell cycle distribution analysis indicates that complex 2 inhibits human carcinoma cells by inducing the cell cycle arrest at the G2/M phase, showing a similar mechanism of action to that of CDDP. The binding interaction of complex 2 with calf thymus DNA (CT-DNA) has been explored by UV-vis absorption and circular dichroism (CD), demonstrating complex 2 has a moderate binding affinity for DNA through intercalation.

Antitumor activity and DNA binding studies on rare earth metal complexes with all-trans retinoic acid andl-glutamic acid

Four new complexes have been synthesized by the reaction of rare earth (III) nitrate with all-trans retinoic acid as the first ligand and L-glutamic acid as the second ligand in an alcoholic solution (pH = 6.5–7.0) with the aim to develop new antitumor drugs. The composition of the complexes has been characterized by elemental analysis, molar conductivity, IR spectroscopy, 1H NMR spectroscopy, thermogravimetric analysis and UV-vis methods. The general molecular formula of the complexes was determined to be REL2L′ (RE = Nd, Eu, La, Sc, L = all-trans retinoic acid, L′ = L-glutamic acid). The antitumor activities of complexes and corresponding ligands were tested by MTT methods. The results indicate that the four rare earth complexes possess different degrees of inhibiting effects on HepG2, A549 and HeLa cells. The suppression ratio of the complexes against the tested tumour cells is superior for the two ligands and RE(III) ions. Especially, the EuL2L′ showed the most obvious antitumor activity on HepG2 and HeLa cells. To investigate the mechanism of inhibition of the complexes, EuL2L′ reacting with DNA was studied by fluorescence spectra, viscosity, UV and CD spectra, and the results showed that the mode of interaction was mainly by intercalation, which may be the one of the important reasons for the highest antitumor activity of the EuL2L′ complex. The results obtained in this study provide certain ideas and an experimental basis for the development of highly efficient and rare earth antitumor drugs that have low toxicity.

Synthesis, crystal structure, cytotoxicity and cell apoptosis induction of a copper(II)-based Schiff base complex

A new copper(II) complex, [CuII(ClQP)(NO3)(H2O)] (1), bearing with 4-Chloro-2-(quinolin-8-yliminomethyl)-phenol (HClQP) as Schiff base ligand, was synthesized and structurally characterized by IR, elemental analysis, ESI-MS and single crystal X-ray diffraction analysis. The crystal structure revealed that complex 1 was five coordinated by one N,N,O-tridentated ClQP, one H2O and one nitrate anion, respectively, to form a pyramidal coordinating geometry. The antitumor activity of complex 1 against HepG2, BEL-7404, MGC80-3 and NCI-H460 tumor cell lines were screened by MTT assay. The IC50 values were in the range of 6.53–23.62μM, in which HepG2 cell line showed the highest sensitivity to complex 1. It is worth noting that complex 1 did not show cytotoxicity to human normal liver cell line HL-7702, suggesting its cytotoxic selectivity on these tumor cell lines. Towards the most sensitive HepG2 cell line, complex 1 significantly induced S phase cell cycle arrest, probably due to its intercalative binding with DNA based on its rigid planar structure as well as the planar aromatic groups of HClQP ligand. Furthermore, the HepG2 cells treated with 1 showed typical cell apoptosis in dose-dependent manner visualized by Hoechst 33258 staining. And the cell apoptosis in the HepG2 cells induced by 1 was further confirmed by the loss of mitochondrial membrane potential visualized by JC-1 staining in cells. The detailed flow cytometric assay revealed that complex 1 could up-regulate the expression of the caspase-3. From these results, it can be concluded that complex 1 induced the mitochondrion-mediated cell apoptosis by caspase-3 activation, most probably due to the S phase cell cycle arrest in HepG2 cells owing to the DNA binding affinity of 1via intercalative binding mode.

Stabilization of Telomere DNA, and Mechanism of Apoptosis of Tumor Cells Induced by Ruthenium Complexes

Telomerase is highly expressed in tumor cells, which has become an important target of anticancer drugs. Since many tumor cells were rich in G4-DNA, we investigated the capabilities of these two ruthenium complexes to stabilize G4-DNA. Two ruthenium(II) complexes were synthesized and characterized via electrospray ionization-mass spectrometry. Since many tumor cells were rich in G4-DNA, we investigated the capabilities of these two ruthenium complexes to stabilize G4-DNA. The interactions of these compounds with G-quadruplex DNA have been studied by fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The stabilization of quadruplex DNA to complex 2 was better than complex 1, and complex 2 can induce telomeric G-quadruplex to occur conformation transformation, while complex 1 cannot. The results showed that the interaction of ruthenium complexes with G-quadruplex DNA was related with the plane of ligand. A novel visual method has been developed for making a distinction between ct-DNA and HTG21 by our Ru complexes binding hemin to form the hemin-G-quadruplex DNAzyme. The results showed that in the presence of complex 1 or 2, HTG21 can fold into a G-quadruplex, but CT-DNA cannot form the G-quadruplex structure. The anticancer activities of these complexes were evaluated by using the MTT assay. Interestingly, the anti-tumor activity of complex 2 exhibited greater inhibition to HepG2 cells, suggesting the ruthenium complexes were much less toxic towards normal cells, and speculated that it targeted the telomeric G-quadruplex was play a role on anti-tumor effect. To further evaluate the characteristics of the death induced by complexes 1 and 2-treated cells staining with Hoechst is analyzed by fluorescence microscopy. These results indicated that complex 2 revealed antiproliferative activities by apoptosis. We also used PI staining and flow cytometry to assess whether the ruthenium complex 2 affected cell cycle progression in HepG2 cells. Complex 2 is a potential antitumor drugs that can induce cancer cell death by acting on cell cycle arrest in G1 phase and the formation of DNA fragments (apoptosis characteristics).

A series of organotin(IV) complexes based on (E)-3-(3-nitrophenyl) acrylic acid: Syntheses, crystal structures and biological activities

A series of organotin carboxylates based on (E)-3-(3-nitrophenyl) acrylic acid (HL), namely {[Ph3SnL]·0.5C6H6}n (1), [(Ph3Sn)2O(L)(Ph3Sn)(L)]n (2) and [Bu2LSnOSnLBu2]2 (3), have been synthesized. All the complexes have been characterized by elemental analysis, IR, 1H NMR spectroscopy and X-ray diffraction analyses. The structural analyses show that complexes 1–2 adopt 1D polymeric chain structures generated by the bridging carboxylate ligands and the five-coordinated tin centers. The structure of complex 3 is centro-symmetric and features a central rhombus Sn2O2 unit with two additional tin atoms linked at the O atoms. In addition, the antitumor activity of complex 3 has been studied.

Nucleic Acid Binding Behavior and Cytotoxicity Properties of a Ruthenium(II) Polypyridyl Complex

The binding of [Ru(IP)2(dppz-11-CO2Me)]2+ (1) {IP = imidazo[4,5-f][1,10]phenanthroline, dppz-11-CO2Me = dipyrido[3,2-a:2′,3′-c]phenazine-11-carboxylic acid methyl ester} to calf thymus DNA and yeast tRNA has been investigated by UV–Vis spectroscopy, fluorescence spectroscopy, viscosity, as well as equilibrium dialysis and circular dichroism. In addition, the antitumor activities of complex 1 have been evaluated by the MTT method. On the basis of the spectroscopic results, the binding mode of complex 1 to CT-DNA and yeast tRNA is intercalation. However, DNA binding with complex 1 is stronger than RNA binding with complex 1, and complex 1 is a better candidate for an enantioselective binder to CT-DNA than to yeast tRNA. These results indicate that the structures of DNA and RNA have significant effects on the binding behaviors of complex 1. Furthermore, complex 1 demonstrates different antitumor activities against selected cancer cell lines in vitro.

Metal and structure tuned in vitro antitumor activity of benzimidazole-based copper and zinc complexes

Four new complexes, Cu2(p-2-bmb)2Cl4 (1), Cu2(p-2-bmb)2Br4 (2), Zn2(p-3-bmb)2Cl4 (3), and [Cu3(p-3-bmb)2Cl4·(CH3OH)2] n (4), have been synthesized under solvothermal reactions based on V-shaped flexible ligands 1-((2-(pyridin-2-yl)-1H-benzoimidazol-1-yl)methyl)-1Hbenzotriazole (p-2-bmb) and 1-((2-(pyridin-3-yl)-1H-benzoimidazol-1-yl)methyl)-1Hbenzotriazole (p-3-bmb). Complexes 1–3 are binuclear, whereas 4 is an infinite chain with trimetallic units, and then these complexes are further extended into 3D supramolecular architectures by π…π interactions and hydrogen bonds. In vitro antitumor activities of these complexes on four human tumor cell lines (gastric tumor cell line, esophagus tumor cell line, liver tumor cell line, colon tumor cell line) were evaluated by MTT assay. The results exhibit that these complexes inhibit the growth of cancer cells by inducing apoptosis, and the inhibition effect shows time- and dose-effect relationship.

Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]: a light-activated antitumor platinum complex that kills human cancer cells by an apoptosis-independent mechanism.

Photoactivatable Pt(IV) diazido complexes have unusual photobiologic properties. We show here that trans,trans,trans-[Pt(IV)(N(3))(2)(OH)(2)(py)(NH(3))] complex 3 is a potent photoactivated cytotoxin toward human cancer cells in culture, with an average IC(50) value in 13 cell lines of 55 ± 28 μmol/L after 30 minutes (0.12 mW/cm(2)) photoactivation with UVA, although visible light was also effective. Photoactivated complex 3 was noncross-resistant to cisplatin in 3 of 4 resistant cell lines. Cell swelling but very little blebbing was seen for HL60 cells treated with irradiated complex 3. Unlike cisplatin and etoposide, both of which cause apoptosis in HL60 cells, no apoptosis was observed for UVA-activated complex 3 by the Annexin V/propidium iodide flow cytotometry assay. Changes in the levels of the autophagic proteins LC3B-II and p62 in HL60 cells treated with UVA-activated complex 3 indicate autophagy is active during cell death. In a clonogenic assay with the SISO human cervix cancer cell line, 3 inhibited colony formation when activated by UVA irradiation. Antitumor activity of complex 3 in mice bearing xenografted OE19 esophageal carcinoma tumors was photoaugmented by visible light. Insights into the novel reaction pathways of complex 3 have been obtained from (14)N{(1)H} nuclear magnetic resonance studies, which show that photoactivation pathways can involve release of free azide in buffered solution. Density functional theory (DFT) and time-dependent DFT calculations revealed the dissociative character of singlet and triplet excited states of complex 3, which gives rise to reactive, possibly cytotoxic azidyl radicals.

ChemInform Abstract: Synthesis, Reactions with DNA, and Antitumor Activity of Platinum Complexes with Aminonitroxyl Radicals

AbstractReview: 40 refs.

Nucleic acid-binding comparative studies and cytotoxic properties of a Ru(II) complex

The comparative studies on the interaction of a ruthenium(II) complex [Ru(IP)2DPBPD(NH2)2]2+ (1) {IP = imidazole[4,5-f] [1,10] phenanthroline, DPBPD(NH2)2 = 2,4,5,6-tetraaminopyrimidine-[3,2-a:2′,3′-c]-phenazine} with CT-DNA (calf thymus DNA) and yeast tRNA have been investigated by different spectrophotometric methods and viscosity measurements. The antitumor activities of complex 1 have been evaluated by MTT {MTT = (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} method. On the basis of the spectroscopic results, the binding mode of complex 1 to CT-DNA and yeast tRNA are intercalation, and RNA binding of complex 1 is stronger than DNA binding. Furthermore, complex 1 is a better candidate for an enantioselective binder to yeast tRNA than to CT-DNA. The results can be explained by the different structure and configuration between CT-DNA and yeast tRNA reasonably, suggesting that the configuration and structure of nucleic acids have significant effects on the binding behaviors of metal complexes. On the other hand, the complex demonstrates different antitumor activity against selected tumor cell lines in vitro.

Chiral self-assembly of triorganotin complexes: Syntheses, characterization, crystal structures and antitumor activity of organotin(IV) complexes containing ( R)-(+)-methylsuccinic acid, ( S)-(+)-methylglutaric acid and l-(−)-malic acid ligands

Six new chiral triorganotin(IV) complexes, {(R 3Sn) 2[C 3H 6(COO) 2]} n (R = Me: 1; Bu: 2), {(R 3Sn) 2[C 4H 8(COO) 2]} n (R = Me: 3; Bu: 4), and {(R 3Sn) 2[C 2H 4O(COO) 2]} n (R = Me: 5; Bu: 6) have been prepared by treatment of ( R)-(+)-methylsuccinic acid, ( S)-(+)-methylglutaric acid and l-(−)-malic acid, with the corresponding R 3SnCl (R = Me, Bu) and sodium ethoxide in methanol. All the complexes were characterized by elemental analysis, FT-IR, NMR ( 1H, 13C, 119Sn) spectroscopy and TGA. Except for 3, all of the complexes were also characterized by X-ray crystallography. The structural analyses reveal that complexes 1 and 5 have 2D network structures in which ( R)-(+)-methylsuccinic acid and l-(−)-malic acid act as tetradentate ligands coordinated to trimethyltin(IV) ions. Complexes 2 and 4 have 3D metal–organic framework structures in which the deprotoned acids serve as tetradentate ligands. Complex 6 adopts a 1D zigzag chain structure and forms a 2D supramolecular framework through intermolecular C–H⋯O interactions. In addition, the antitumor activities of complexes 1– 6 have been studied. We also have measured the specific rotation of the chiral dicarboxylic acids and the organotin derivatives.

Synthesis, reactions with DNA, and antitumor activity of platinum complexes with aminonitroxyl radicals

The work is a review of the data on the synthesis of mono- and biradical PtII complexes with mono- and diaminonitroxyl radicals, as well as of a binuclear complex with diaminonitroxyl radical. A “mild” method is considered for the synthesis of a number of PtIV nitroxyl complexes (9–11), whose lipophilicity varies within a wide range due to the trans-ligands, i.e., the linear aliphatic acid moieties. Correlations between the structures of the complexes, efficiency of their binding to DNA, and the effect of this binding on the DNA stability were established. Cytotoxic properties of the complexes against the HeLa, H1299, and MCF7 tumor cells, the effect of the complexes on the cell cycle, and the p53 protein expression were studied. The data on the antitumor activity of the complexes in the animal tumor model, P388 leukemia, are given. The rate of the development of resistance to complex 10a for P388 leukemia is 2.5 times lower than the corresponding value for cisplatin. It was found that a synergistic enhancement of antitumor activity is observed when low doses of cisplatin and complexes 9b or 10b are simultaneously administered. The specificities of biological activity of the platinum nitroxyl complexes are presumably due to the antioxidant properties of the nitroxyl pharmacophore and the ability of these complexes to cause the p53-independent tumor cell death.

Synthesis, characterization, crystal structure and antitumor activity of organotin(IV) compounds bearing ferrocenecarboxylic acid

Four new organotin(IV) complexes [(Bu3Sn)(FcCOO)]n (1), [(μ-Bu2Sn)2(μ-Bu2SnFcCOO)2(μ3-O)2(μ-OCH3)2]2 (2), [Ph3Sn(FcCOO)(H2O)](phen) (3) and [{Ph3Sn(FcCOO)}2(4,4′-bipy)] (4) [Fc=(η5-C5H5)Fe(η5-C5H4)] have been synthesized and characterized by elemental analyses, IR, (1H and 13C) NMR spectra and X-ray single-crystal diffraction analyses. The structure analyses show that all tin atoms in complexes 1–4 are five-coordinated with trigonal bipyramid geometry. Complexes 1–4 and FcCOOH undergo reversible one-electron oxidations in methanol solution. The antitumor activities of complexes 1–4 have also been tested. Complexes 1 and 2 exhibit medium activity towards P388 cell lines and Hela cell lines. Complexes 3 and 4 exhibit medium activity towards P388 cell lines but strong activity towards Hela cell lines. This may result from complexes 3 and 4 including the neutral molecules 1,10-phenanthroline and 4,4′-bipy.

Macrocyclic organotin(IV) carboxylates based on benzenedicarboxylic acid derivatives: Syntheses, crystal structures and antitumor activities

Six new organotin carboxylates based on 1,3-benzenedicarboxylic acid and 1,4-benzenedicarboxylic acid derivatives, namely (Ph 3Sn) 2(2,5-L 1)(C 2H 5OH) 2 ( 1) (2,5-H 2L 1 = 2,5-dibenzoylterephthalic acid), (Ph 3Sn) 2(2,5-L 2)(C 2H 5OH) 2 ( 2) (2,5-H 2L 2 = 2,5-bis(4-methylbenzoyl)terephthalic acid), (Ph 3Sn) 2(2,5-L 3)(C 2H 5OH) 2 ( 3) (2,5-H 2L 3 = 2,5-bis(4-ethylbenzoyl)terephthalic acid), [( n-Bu 2Sn) 4(4,6-L 1)O 2(OH)(OC 2H 5)] 2·2(C 2H 5OH) ( 4) (4,6- H 2L 1 = 4,6-dibenzoylisophthalic acid), [( n-Bu 2Sn) 4(4,6-L 1)O 2(OH)(OC 4H 9)] 2·2(C 4H 9OH) ( 5) and [( n-Bu 2Sn) 4(4,6-L 2)O 2(OH)(OC 2H 5)] 2·2(C 2H 5OH) ( 6) (4,6-H 2L 2 = 4,6-bis(4-methylbenzoyl)isophthalic acid), have been synthesized. All the organotin carboxylates have been characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy and X-ray crystallography diffraction analyses. The structural analysis reveals that complexes 1– 3 show similar structures, containing binuclear triorganotin skeletons. The significant intermolecular O–H⋯O hydrogen bonds linked the complexes 1– 3 to form a novel 2D network polymer with 38-member macrocycles. In complexes 4– 6, two Sn 4O 4 ladders are connected by two 1,3-benzenedicarboxylic acid derivatives to yield ladder-like octanuclear architectures and form macrocycle with 24 atoms. In addition, the antitumor activities of complexes 1– 6 have been studied.

Palladium(II) complexes of quinolinylaminophosphonates: Synthesis, structural characterization, antitumor and antimicrobial activity

Three types of palladium(II) halide complexes of quinolinylaminophosphonates have been synthesized and studied. Diethyl and dibutyl [α-anilino-(quinolin-2-ylmethyl)]phosphonates ( L1, L2) act as N, N-chelate ligands through the quinoline and aniline nitrogens giving complexes cis-[Pd( L1/L2) X 2] (X═Cl, Br) ( 1–4). Their 3-substituted analogues [α-anilino-(quinolin-3-ylmethyl)]phosphonates ( L3, L4) form dihalidopalladium complexes trans-[Pd( L3/L4) 2X 2] ( 5–8), with trans N-bonded ligand molecules only through the quinoline nitrogen. Dialkyl [α-(quinolin-3-ylamino)- N-benzyl]phosphonates ( L5, L6) give tetrahalidodipalladium complexes [Pd 2( L5/L6) 3X 4] ( 9–12), containing one bridging and two terminal ligand molecules. The bridging molecule is bonded to the both palladium atoms, one through the quinoline and the other through the aminoquinoline nitrogen, whereas terminal ligand molecules are coordinated each only to one palladium via the quinoline nitrogen. Each palladium ion is also bonded to two halide ions in a trans square-planar fashion. The new complexes were identified and characterized by elemental analyses and by IR, UV–visible, 1H, 13C and 31P nuclear magnetic resonance and ESI-mass spectroscopic studies. The crystal structures of complexes 1–4 and 6 were determined by X-ray structure analysis. The antitumor activity of complexes in vitro was investigated on several human tumor cell lines and the highest activity with cell growth inhibitory effects in the low micromolar range was observed for dipalladium complexes 11 and 12 derived from dibutyl ester L6. The antimicrobial properties in vitro of ligands and their complexes were studied using a wide spectrum of bacterial and fungal strains. No specific activity was noted. Only ligands L3 and L4 and tetrahalidodipalladium complexes 9 and 11 show poor activities against some Gram positive bacteria.