Effect of cobalt(II) complexes with dipyridylamine and salicylaldehydes on cultured tumor and non-tumor cells: Synthesis, crystal structure investigations and biological activity (original) (raw)
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The synthesis, physico-chemical characterization and cytotoxicity against five human tumoral cell lines (THP-1, U937, Molt-4, Colo205 and H460) of three new cobalt(II) coordination compounds are reported (i.e. Co(HL1)Cl (1), Co(HL2)Cl (2) and [Co(HL3)Cl]0.0.5 (CH 3) 2 CHOH (3)). H 2 L2 (2-{[[2-hydroxy-3-(1-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol) and H 2 L3 (2-{[[2-hydroxy-3-(2-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol) present α and β-naphthyl groups respectively, which is absent in H 2 L1 (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]propylamine. These compounds were characterized by a range of physico-chemical methods. X-ray diffraction studies were performed for complex (3), indicating the formation of a mononuclear complex. Complexes (2) and (3), which contain α and β-naphthyl groups respectively, have presented lower IC 50 values than those exhibited by complex (1). Complex (3) presents IC 50 values lower than cisplatin against Colo205 (90 and 196 μmol L −1 , respectively) and H460 (147 and 197 μmol L −1 , respectively). These human neoplastic cells under investigation were also more susceptible toward complex (3) than peripheral blood mononuclear cells. Transmission electron microsco-py investigations are in agreement with the loss of mitochondrial membrane potential (ΔΨm) observed by JC-1 mitochondrial potential sensor and indicate that the activity of complex (3) against leukemic cell line (U937) is mediated by an apoptotic mechanism associated with mitochondrial dysfunction (intrinsic pathway).
Journal of Inorganic Biochemistry, 2008
The structures and spectroscopic properties of new Mn(II), Co(II), Cd(II), Hg(II), Ag(I), Rh(III), and Ir(I) complexes with the ligand BZLMH derived from 6-acetyl-1,3,7-trimethyllumazine (lumazine = pteridine-2,4(1H,3H)-dione) and benzohydrazide are reported. Complexes have been characterized by elemental analyses, spectroscopic studies (IR, UV-vis, 1 H, 13 C and 15 N NMR) and magnetic measurements. In all the complexes, the lumazine-derived ligand appears to be coordinated in either tridentate (N5, N61 and O63) or tetradentate forms (O4, N5, N61 and O63). The molecular structures of the [Co(BZLMH)-(H 2 O)(CH 3 CN) 2 ](ClO 4) 2 Á CH 3 CN and [RhCl 2 (BZLM)(CH 3 CN)] Á CH 3 CN complexes, determined by single crystal X-ray diffraction, have allowed to corroborate both coordination behaviours. The cytotoxic activity of the free ligand and complexes against human neuroblastoma NB69 cell line is also described. The differential analysis of the initial cytotoxic screening data has shown good activity only for the [RhCl 2 (BZLM)(CH 3 CN)] Á CH 3 CN compound at concentrations at around 2 lM; for the other complexes, a modulation of the cell growth was not found upon complexation, this non-specific effect strongly suggesting an apoptotic behaviour.
Bioinorganic Chemistry and Applications, 2008
Recommended by Lorenzo Pellerito (6-(cyclohexylamino)-1,3-dimethyl-5(2-pyridyl)furo[2,3-d]pyrimidine-2,4(1H,3H)-dione) abbreviated as CDP was synthesized and characterized. Ti(IV), Zn(II), Fe(III), and Pd(II) metal complexes of this ligand are prepared by the reaction of salts of Ti(IV), Zn(II), Fe(III), and Pd(II) with CDP in acetonitrile. Characterization of the ligand and its complexes was made by microanalyses, FT-IR, 1 H NMR, 13 C NMR, and UV-Visible spectroscopy. All complexes were characterized by several techniques using elemental analysis (C, H, N), FT-IR, electronic spectra, and molar conductance measurements. The elemental analysis data suggest the stoichiometry to be 1:1 [M:L] ratio formation. The molar conductance measurements reveal the presence of 1:1 electrolytic nature complexes. These new complexes showed excellent antitumor activity against two kinds of cancer cells that are K562 (human chronic myeloid leukemia) cells and Jurkat (human T lymphocyte carcinoma) cells.
Scientific Reports, 2019
Two cobalt(III) Schiff base complexes, trans-[Co(salen)(DA) 2 ](Clo 4) (1) and trans-[Co(salophen)(DA) 2 ] (Clo 4) (2) (where salen: N,N'-bis(salicylidene)ethylenediamine, salopen: N,N'-bis(salicylidene)-1,2phenylenediamine, DA: dodecylamine) were synthesised and characterised using various spectroscopic and analytical techniques. The binding affinity of both the complexes with CT-DNA was explored adopting UV-visible, fluorescence, circular dichroism spectroscopy and cyclic voltammetry techniques. The results revealed that both the complexes interacted with DNA via intercalation as well as notable groove binding. protein (BsA) binding ability of these complexes was investigated by absorption and emission spectroscopy which indicate that these complexes engage in strong hydrophobic interaction with BSA. The mode of interaction between these complexes and CT-DNA/BSA was studied by molecular docking analysis. the in vitro cytotoxic property of the complexes was evaluated in A549 (human small cell lung carcinoma) and VeRo (African green monkey kidney cells). the results revealed that the complexes affect viability of the cells. AO and EB staining and cell cycle analysis revealed that the mode of cell death is apoptosis. Both the complexes showed profound inhibition of angiogenesis as revealed in in-vivo chicken chorioallantoic membrane (CAM) assay. of the two complexes, the complex 2 proved to be much more efficient in affecting the viability of lung cancer cells than complex 1. These results indicate that the cobalt(III) Schiff base complexes in this study can be potentially used for cancer chemotherapy and as inhibitor of angiogenesis, in general, and lung cancer in particular, for which there is need for substantiation at the level of signalling mechanisms and gene expressions. Metal-based therapeutics have become a viable area of research in medicinal chemistry after the serendipitous discovery of cis-platin. At present nearly half the number of cancer patients are treated with platinum-based drugs 1,2. However, platinum-based drugs are associated with (i) adverse side effects, (ii) lack of selectivity and (iii) intrinsic or acquired resistance, which prompted search for effective non-platinum drugs. Over the years, complexes of Ru, Ir, Cu, Ni, Zn, Co, etc., have been reported to posses much better anticancer property than cis-platin 3-6. Cobalt is an essential trace element present in the human body. It is involved in important biological functions such as fatty acid and amino acid metabolism, haematopoiesis, and, in the form of vitamin B 12 it is
Selective Cytotoxicity of Complexes with N,N,N-Donor Dipodal Ligand in Tumor Cells
International Journal of Molecular Sciences
The present article demonstrates selective cytotoxicity against cancer cells of the complexes [Co(LD)2]I2∙CH3OH (1), [CoLD(NCS)2] (2) and [VOLD(NCS)2]∙C6H5CH3 (3) containing the dipodal tridentate ligand LD = N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)amine), formed in situ. All tested complexes expressed greater anticancer activities and were less toxic towards noncancerous cells than cisplatin. Cobalt complexes (1 and 2) combined high cytotoxicity with selectivity towards cancer cells and caused massive tumour cell death. The vanadium complex (3) induced apoptosis specifically in cancer cells and targeted proteins, controlling their invasive and metastatic properties. The presented experimental data and computational prediction of drug ability of coordination compounds may be helpful for designing novel and less toxic metal-based anticancer species with high specificities towards tumour cells.
Ternary complexes of Co (II), Ni (II), Cu (II) and Zn (II) with glutamic acid (glu) as a primary ligand and leucine (leu) or valine (val) as secondary ligand were prepared in slightly acidic medium. The structures of the complexes were elucidated using elemental, IR, mass spectra, magnetic moment, UV–Vis spectrophotometer and thermal analyses. The ternary complexes were isolated in 1:1:1 molar ratio and the molecular structures were found to be M(glutamic)(leucine)(H 2 O) 2 ] H 2 O and [M(glutamic) (valine)(H2O)2].H2O, where M = Co(II), Ni(II). Thermogravimetric analysis confirmed that two water molecules coordinated to the central metal atom and one crystalline water molecule. UV–Vis spectra showed that the complexes have octahedral symmetry. On the other side, ternary copper complexes with molecular formula [Cu(glu)(leu)] and [Cu(glu)(val)] where the two amino acids coordinated using oxygen and nitrogen forming distorted square planar structure as further supported by electron spin resonance ESR spectra. The ternary zinc complexes showed that the glutamic acid acted as tridentate ligand while leucine or valine acted as monodentate ligands. Moreover, the ligands and their metal complexes were screened against bacteria and fungi using the inhibitory zone diameter. Furthermore, the complexes were tested their cytotoxicity effects against three types of human cancer cell lines hepatocellular carcinoma (HePG2), human colonic carcinoma (HCT) and breast cancer cell lines (MCF-7).
The development of new medicines for the successful treatment of cervical and liver malignancies is critical in order to address the disadvantages of current chemotherapeutics, such as increased resistance. Metal ion-based chemical complexes have recently emerged as a prominent method for cancer therapy. As a result, the study aims to create novel anticancer medicines based on leads acquired through combinatorial chemistry of metal complexes. Cobalt (III) Schiff base trans- [Co(salen)(DA)2](ClO4) (complex 1) and trans-[Co (salophen)(DA)2](ClO4) (complex 2)] where, the salen and salopen were N, N′-bis(salicylidene) ethylenediamine, and N, N′-bis(salicylidene)-1,2- phenylenediamine, DA: dodecylamine) were synthesized as an alternative to the existing drugs, and their cytotoxic effect were evaluated against human cervical (HeLa) and liver cancer cell lines (HepG2) using MTT viability assay, and apoptotic morphological staining which including Acridine Orange/Ethidium Bromide (AO/EB), H...
Trakia Journal of Sciences, 2019
PURPOSE. The aim of this study was to evaluate cytotoxic / antitumor properties of newly synthesized metal [Zn(II), Cu(II), Co(II), Ni(II), Zn(II)/Ag(I), Zn(II)/Au(I)] complexes with various ligands (Schiff bases, non-steroidal anti-inflammatory drugs, bile acids) and to introduce an optimized strategy for such investigations in our research activity. MATERIALS AND METHODS. Human and animal tumor and non-tumor cells were used as model systems. Short-term (3 – 96h) and long-term (> 2 weeks) experiments were carried out using cytotoxicity assays, cytological / immunocytochemical, biochemical and molecular-biological methods to assess the influence of the compounds on cell viability and proliferation and their ability to induce apoptosis/necrosis and/or autophagy. RESULTS. The examined metal complexes express cytotoxic activity that is time- and concentration-dependent and are more active than the corresponding ligands tested alone. Zn(II)/Au(I) and Zn(II)/Ag(I) complexes with Salen...
TURKISH JOURNAL OF BIOLOGY, 2014
Introduction Cancer is considered the second most common disease causing death (Tuncer, 2008). It is estimated that 19.3 million new cancer cases will be detected per year by 2025. The incidence, morbidity, and mortality of cancer are expected to be much higher in developing countries such as Turkey. Efforts to cure cancer or reduce its occurrence will be significantly important (Tuncer, 2008). Although many anticancer drugs have been used to treat cancer, they have some limitations, such as side effects, tumor specificity, and tumor cell resistance (Roche, 2002). Therefore, new anticancer drug candidates with few or no side effects need to be developed as alternatives to current chemotherapeutic drugs. Metals and metal compounds have been used in medicine as antiprotozoal, antiulcer, antiarthritic, antimalarial, antimicrobial, and anticancer drugs (Avendańo, 2008). Nowadays, the application of metal complexes in medicine is being investigated very extensively. Thati et al. (2007) reported that silver complexes of coumarin derivatives possess anticancer activity against certain types of cancer. Zhu et al. (2003) reported that silver carboxylate dimers exert anticancer activity against human carcinoma cells. The phosphine Abstract: The discovery of anticancer activity in cisplatin triggered the development of novel drugs containing metals such as platinum or ruthenium. Extremely diverse structural chemistry and the interaction of metal complexes with biomolecules resulted in the exploration of novel metal complexes with drug potential. In the present study, the anticancer and cytotoxic activities and the mechanisms of action were investigated for C 16 H 34 N 8 O 5 Ag 2 Cd (AN1) and C 11 H 16 N 7 O 2 Ag 3 Ni (AN7), 2 newly synthesized dicyanidoargentate(I) complexes. The anticancer and cytotoxic activities of AN1 and AN7 on several cancer cell lines were tested by cell proliferation and cytotoxic activity assays, respectively. The apoptotic and replication inhibitory potentials of the compounds were investigated using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) and DNA topoisomerase inhibition assays. AN1 and AN7 showed significant (P < 0.05) anticancer activity and lower cytotoxicity against all cell lines tested. The TUNEL assay results indicated that AN1 and AN7 may inhibit cell proliferation by inducing apoptosis. The compounds showed very significant DNA topoisomerase I inhibitory activity. Based on the results, it is suggested that compounds AN1 and AN7 are potential anticancer drug candidates.
Applied Organometallic Chemistry, 2017
Thiosemicarbazone ligand, 2-((4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromen-6-yl) methylene) hydrazinecarbothioamide and its Cd(II), Cu(II), Zn(II), Ni(II), Co(II), VO(II), and Mn(II) complexes have been prepared and characterized by various spectroscopic and analytical techniques. Complexes molar conductance measurements displayed that all complexes (2-8) are non-electrolyte. With general composition [M(H 3 L)(CH 3 COO) 2 H 2 O].nH 2 O, where M = Cd(II), Cu(II), Zn(II), Ni(II), Co(II) and Mn(II) while complex (8) has [VO(H 3 L)(SO 4)H 2 O].2H 2 O formula. Based on analytical and spectral measurements, the octahedral or distorted octahedral geometries suggested for complexes. Ligand and complexes anti-proliferative activities were assessed against three various human tumor cell lines including breast cancer (MCF-7), liver cancer (HepG2) and lung cancer (A549) using SRB fluorometric assay and cis-platin as positive control. The anti-proliferative activity result indicated that the ligand and its complexes have considerable anti-proliferative activity analogous to that of ordinarily utilized anti-cancer drug (cis-platin). They do their anti-cancer activities by modifying free radical's generation via raising the superoxide dismutase activity and depletion of intracellular reduced glutathione level, catalase, glutathione peroxidase activities, escorted by highly generation of hydrogen peroxide, nitric oxide and other free radicals leading to tumor cells death, as monitoring by decreasing the protein and nucleic acids synthesis.