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In this paper, a series of new ruthenium complexes of the general formula [Ru(NS)(dpphpy)(dppb)]PF6 (Ru1-Ru3), where dpphpy = diphenyl-2-pyridylphosphine, NS ligands = 2-thiazoline-2-thiol (tzdt, Ru1), 2-mercaptopyrimidine (pySm, Ru2), and 4,6-diamino-2-mercaptopyrimidine (damp, Ru3), and dppb = 1,4-bis(diphenylphosphino)butane, were synthesized and characterized by elemental analysis, spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and X-ray diffraction. In the characterization, the correlation between the phosphorus atoms and their respective aromatic hydrogen atoms of the compounds in the assignment stands outs, by 1H-31P HMBC experiments. The compounds show anticancer activities against A549 (lung) and MDA-MB-231 (breast) cancer cell lines, higher than the clinical drug cisplatin. All of the complexes are more cytotoxic against the cancer cell lines than against the MRC-5 (lung) and MCF-10A (breast) nontumorigenic human cell lines. For A549 tumor cells, cell cycle analysis upon treatment with Ru2 showed that it inhibits the mitotic phase because arrest was observed in the Sub-G1 phase. Additionally, the compound induces cell death by an apoptotic pathway in a dose-dependent manner, according to annexin V-PE assay. The multitargeted character of the compounds was investigated, and the biomolecules were DNA, topoisomerase IB, and proteasome, as well as the fundamental biomolecule in the pharmacokinetics of drugs, human serum albumin. The experimental results indicate that the complexes do not target DNA in the cells. At low concentrations, the compounds showed the ability to partially inhibit the catalytic activity of topoisomerase IB in the process of relaxation of the DNA plasmid. Among the complexes assayed in cultured cells, complex Ru3 was able to diminish the proteasomal chymotrypsin-like activity to a greater extent.

In this study, we report on the selective esterification of the carboxyl group in a coordinated ligand based on the Fischer reaction. The new [Ru(N–O)(bipy)(dppb)]PF6 complex 1 was used as a precursor to obtain the ester derivative [Ru(N–Oet)(bipy)(dppb)]PF6 (2), and in order to establish the influence of either the free carboxyl group or the ethoxycarbonyl group on biological properties, the [Ru(pic)(bipy)(dppb)]PF6 complex (3) was synthesized for comparison (dppb = 1,4-bis(diphenylphosphino)butane, bipy = 2,2′-bipyridine, N–O = mono-deprotonated 2,4-pyridinedicarboxylic acid, N–Oet = 4-ethoxycarbonyl-2-pyridinecarboxylic acid). All three complexes interact weakly with human serum albumin (HSA) with Kb values ranging from 101–104 M−1, suggesting a spontaneous interaction with this protein by electrostatic (1–2) or van der Waals interactions (3). Moreover, complex/DNA-binding experiments indicate that complexes 2 and 3 interact weakly with DNA, while no interaction is observed between complex 1 and DNA, probably due to the repulsion involving the free carboxylate group/DNA-phosphate. Anti-Mycobacterium tuberculosis (MTB) activity and cytotoxicity assays against one normal cell line V79 (hamster fibroblast) and three human cancer cell lines A549 (lung), MCF7 and MDA-MB-231 (breast) revealed that complexes 2 and 3 exhibit good activity against MTB and tumor cells, presenting high cytotoxicity (low IC50). On the other hand, complex 1 is practically inactive. Therefore, the best biological results found for complex 2 can be attributed to its esterification, improving the lipophilicity and cellular uptake, in order to facilitate its passive permeation through the tumor cell membranes allowing for cell death, as well as DNA and HSA interactions, when compared with complex 1.

Four new organoruthenium complexes with formula [RuCl(η6-p-cymene)(μ-FCZ)]2[Cl]2 (1), [RuCl(FCZ)(η6-p-cymene)(PPh3)]PF6 (2), [RuCl(CTZ)(η6-p-cymene)(PPh3)]PF6 (3) and [RuCl(KTZ)(η6-p-cymene)(PPh3)]PF6 (4) (where FCZ: 2-(2,4-difluorophenyl)-1,3-di(1H-1,2,4-triazol-1-yl)-2-propanol, CTZ: 1-[(2-chlorophenyl)-diphenylmethyl-1H-imidazole] and KTZ: cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) were synthesized, characterized and evaluated as potential inhibitors for Leishmania amazonensis growth by widely reported methods. Complexes 3 and 4 displayed effective IC50 activities against Leishmania amazonensis promastigotes and intracellular amastigotes in the range of nanomolar concentration. Scanning and transmission electron microscopy analysis of Leishmania amazonensis promastigotes after treatment with 300 or 500 nM of complexes 3 and 4 for 48 h showed morphological alterations in the cell surface, a shortening of the flagellum, loss of mitochondrial matrix, disorganization of the kDNA and abnormal chromatin condensation. Thus, our strategy of incorporating a ruthenium atom into the structure of clinical drugs to improve their efficacy continues to demonstrate suitability for metallodrug discovery purposes.

A series of five new ruthenium phosphine/diimine complexes were prepared and characterized by IR, UV–Vis, 1H, 31P{1H} and 13C{1H} NMR spectroscopies, elemental analyses and cyclic voltammetry. Four of the complexes have the general formula ct-[RuCl(L)(dppb)(4,4′-Mebipy)](PF6)n (dppb = 1,4-bis(diphenylphosphino)butane, 4,4′-Mebipy = 4,4′-dimethyl-2,2-bipyridine and L = CO, NO+, NO2− or pyridine), and one has the formula [Ru(NO3)(dppb)(4,4′-Mebipy)]PF6, where NO3− is a bidentate ligand. In addition, the crystal structure of the complex ct-[RuCl(CO)(dppb)(4,4′-Mebipy)]PF6 was elucidated by single-crystal X-ray diffraction analysis, which supported the geometry of the compounds suggested by the 31P NMR experiments. The cytotoxic activity of the synthesized compounds was evaluated against five cancer cell lines: HepG2 (liver), HT144 (melanoma), A549 (lung), MDA-MB-231 (breast) and HCT-9 (colon). Human serum albumin (HSA) and DNA binding experiments were also conducted. The HSA binding constants and thermodynamic parameters suggested spontaneous interactions of the complexes with this protein through van der Waals forces and hydrogen bonding. A spectroscopic titration study indicated that the compounds interacted with ct-DNA, exhibiting binding constants, Kb, on the order of 1.0 × 104 M−1. Additionally, the ruthenium complex containing pyridine displayed cytotoxic activity against HT144, A549, and MDA-MB-231. In addition, it demonstrated pro-apoptotic activity on MDA-MB-231 cells as well as the ability to reduce colony formation. These findings are very promising and have motivated further studies for identifying the molecular target underlying the antitumor activity of the ruthenium(II)/pyridine complex against triple-negative breast cancer.

The new complexes [Cu(PPh3)2(KTZ)2]NO3 (1), [Cu(PPh3)2(CTZ)2]NO3 (2), [Au(KTZ)2]Cl (3), [Au(CTZ)2]Cl (4) and Pt(KTZ)2Cl2 (5) were prepared by reaction of KTZ, CTZ (where CTZ: 1-[(2-chlorophenyl)-diphenylmethyl]-1H-imidazole and KTZ: cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) and their respective metal salts or metal complexes under mild conditions. They were characterized using NMR, UV-vis and IR spectroscopies, microanalytical analysis and mass spectrometry. Complex (5) was also investigated using computational methods (DFT) to evaluate the geometry configuration around the Pt(II) coordination sphere; the results showed that the trans complex is the most stable one. The antifungal activities of these new compounds 1–5 and some of our reported metal-based azole drug derivatives such as Pt(CTZ)2Cl2 (6), [Au(PPh3)(KTZ)]PF6 (7) and [Au(PPh3)(CTZ)]PF6 (8) were evaluated against sporotrichosis agents (Sporothrix schenckii, Sporothrix brasiliensis and Sporothrix globosa). Their selectivities towards fungal cells were also evaluated. Complexes [Cu(PPh3)2(KTZ)2]NO3 (1), [Cu(PPh3)2(CTZ)2]NO3 (2), [Au(PPh3)(KTZ)]PF6 (7) and [Au(PPh3)(CTZ)]PF6 (8) inhibited fungal growth and killed fungi at concentrations in the nanomolar range and were more active than CTZ or KTZ alone. Microscopy analysis using scanning electron microscopy showed that the complexes 1, 2, 7 and 8 interfered with the cell shape. All the metal–azole complexes tested were more selective for fungi than for mammalian cells and human red blood cells, revealing that they are promising molecules for the development of new antifungal compounds.

Made available in DSpace on 2017-11-28T23:31:23Z (GMT). No. of bitstreams: 1 PSynthesisofthen6pcymene....pdf: 2685420 bytes, checksum: f97966db7a6a6139e07a3179d50eed61 (MD5) Previous issue date: 2017-11-28

Herein syntheses and characterization of the complexes [Pt(PG)(PPh3)2] (1) and [Ru(PG)(dppm)2] (2), where PG (propyl gallate) = propyl 3,4,5-trihydroxybenzoate, PPh3 = triphenylphosphine and dppm = 1,1-bis(diphenylphosphino) methane, are described. The structure of the complex [Pt(PG)(PPh3)2] was elucidated by X-ray diffraction. The cytotoxicity of the complexes against four tumor cell lines, lung carcinoma (A549), breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), glioblastoma (U251MG), and a normal fibroblast (CCD-1059Sk) were evaluated. The selectivity index values showed that complex (2) is more potent and selective than the free propyl gallate molecule and complex (1). Furthermore, complex (2) is a slightly higher active against the tumor cells MCF-7 and HepG2 than the cisplatin. In addition, BSA-binding experiments and antioxidant activity of the complexes were evaluated. The interactions of the complexes with the BSA showed negative ΔH and ΔS values, leading to van der Waals force or hydrogen bond formation between the complexes and the biomolecule. Furthermore, the negative ΔG values reveal that the interaction process of complex/BSA is spontaneous. It was observed that the [Pt(PG)(PPh3)2] complex has an inhibitory effect against free radicals, whereas [Ru(PG)(dppm)2] was not active. Circular dichroism showed that the free ligand and the complexes are unable to modify the DNA secondary structure of this biomolecule.

Made available in DSpace on 2018-12-11T17:03:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-09-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Three ruthenium complexes [RuCl(CTZ)(bipy)(P-P)]PF6 [P-P = 1,2-bis(diphenylphosphino)ethane (dppe-1), 1,4-bis(diphenylphosphino)butane (dppb-2) and 1,1′-bis(diphenylphosphino)ferrocene (dppf-3), bipy = 2,2′-bipiridine and clotrimazole (CTZ) 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole] were synthesized. These complexes were characterized by a combination of elemental analysis, molar conductivity, infrared and UV–vis spectroscopy, 1H, 13C{1H} and 31P{1H} nuclear magnetic resonance techniques, cyclic voltammetry and mass spectroscopy. Bovine serum albumin binding constants, which were in the range of 1.30–36.00 × 104 M− 1, and thermodynamic parameters suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. DNA interactions studied by spectroscopic titration, viscosity measurements, gel electrophoresis, circular dichroism, ethidium bromide displacement and reactions with guanosine and guanosine monophosphate indicated the DNA binding affinity primarily through non-covalent interactions. All complexes 1–3 were tested against the human carcinoma cell lines MCF-7 (breast), A549 (lung) and DU-145 (prostate) presenting promising IC50 values, between 0.50 and 14.00 μM, in some cases lower than the IC50 for the reference drug (cisplatin). The antimicrobial activity assays of the complexes provided evidence that they are potential agents against mycobacterial infections, specifically against Mycobacterium tuberculosis H37Rv. Departamento de Química Universidade Federal de São Carlos-SP Departamento de Gerontologia Universidade Federal de São Carlos-SP Departamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas UNESP Directoria de Metrologia Aplicada a Ciências da Vida Instituto Nacional de Metrologia Qualidade e Tecnologia INMETRO Departamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas UNESP FAPESP: 13/03513-9 CNPq: 141738/2013-8 CNPq: 141739/2013-4

Cu isotope fractionation was investigated in the human neuroblastoma SH-SY5Y cell line, in a proliferating/tumor phase (undifferentiated cells), and in a differentiated state (neuron-like cells), induced using retinoic acid (RA). The SH-SY5Y cell line displays genetic aberrations due to its cancerous origin, but differentiation drives the cell line towards phenotypes suitable for the research of neurological diseases (e.g., Alzheimer’s disease or Parkinson’s disease). Cellular Cu distribution was first explored by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging and, subsequently, Cu isotopic analysis was performed at cellular and sub-cellular levels via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS). The SH-SY5Y cells showed a re-distribution of intracellular Cu upon RA differentiation. Both undifferentiated and differentiated cells became systematically enriched in the light 63Cu isotope with increasing intracellular Cu content. Differentiated neuron-like SH-SY5Y cells showed a heavier Cu isotopic composition (+ 0.3‰) than did the undifferentiated proliferating cells when exposed to Cu for 24 h. However, after a longer exposure time (72 h), no difference was observed between both cellular phenotypes. Mitochondrial fractions were enriched in the light 63Cu isotope, compared to whole cells, for both undifferentiated and differentiated cells (no significant difference). The Cu isotopic composition of the remaining cell lysates was heavier than that of the whole cells and + 0.2‰ heavier in the differentiated cells than in the undifferentiated cells. These results indicate that neuronal differentiation affects the Cu isotope fractionation accompanying Cu uptake in the cells, but this effect does not seem to be associated with the mitochondrial Cu pathway. Cu isotope fractionation can be an interesting tool for studying Cu metabolism at a (sub)-cellular level in functional neurons.

The rational design of anticancer agents that acts in specific biological targets is one of the most effective strategies for developing chemotherapeutic agents. Aiming at obtaining new ruthenium (II) compounds with good cytotoxicity against tumor cells, a series of new complexes of general formula [RuCl(PPh3)(Hdpa)(N N)]Cl [PPh3 = triphenylphosphine, N-N = 2,2′-dipyridylamine (Hdpa) (1), 1,2-diaminoethane (en) (2), 2,2′-bipyridine (bipy) (3), 5,5′-dimethyl-2,2′-bipyridine (dmbipy) (4), 1,10-phenanthroline (phen) (5) and 4,7-diphenyl-1,10-phenanthroline (dphphen) (6)] were synthesized. The complexes were characterized by elemental analysis and spectroscopic techniques (IR, UV/Visible, and 1D and 2D NMR) and three of their X-ray structures were determined: [RuCl(PPh3)(Hdpa)2]Cl, [RuCl(PPh3)(Hdpa)(en)]Cl and [RuCl(PPh3)(Hdpa)(dmbipy)]Cl. All the complexes are more cytotoxic against the cancer cell line than against the non-tumor cell line, highlighting complexes 1 and 5, which have an index selectivity of 18 and 15, respectively. The binding constants of compounds 1–6 with human serum albumin (HSA) were determined by tryptophan fluorescence quenching, indicating moderate to strong interactions. The binding mode of the complexes to calf thymus (CT) DNA was explored by several techniques, which reveal that only the dphphen compound 6 causes distortions in the secondary and tertiary structures of DNA. The studies demonstrated that the nature of the N N co-ligand and the presence of the PPh3 and Hdpa ligands are features that can influence the binding affinity of the complexes by the biomolecules and in the cytotoxic activity of the complexes. Overall, the complexes with diimine co-ligand are much more cytotoxic than compound 2 with the aliphatic diamine.

The efficacy of organoruthenium complexes containing ergosterol biosynthesis inhibitors (CTZ: clotrimazole, KTZ: ketoconazole and FCZ: fluconazole) against tumor cells, and their interaction with important macro-biomolecules such as human serum albumin and DNA have been investigated here. Our experimental results indicated that these ruthenium(II) complexes present spontaneous electrostatic interactions with albumin, and act as minor groove binders with the DNA. The ability of these Ru(II)&ndash, azole complexes to inhibit the proliferation of selected human tumor and non-tumor cell lines was determined by MTT assay. Complexes [RuCl(CTZ)(&eta, 6-p-cymene)(PPh3)]PF6 (3) and [RuCl(KTZ)(&eta, 6-p-cymene)(PPh3)]PF6 (4) were shown to be between 3- and 40-fold more cytotoxic than the free ligands and the positive control cisplatin. Complex 3 was selected to continue studies on the triple negative breast tumor cell line MDA-MB-231, inducing morphological changes, loss of adhesion, inhibition of colony formation, and migration through Boyden chambers, cell cycle arrest in the sub-G1 phase, and a mechanism of cell death by apoptosis. All these interesting results show the potential of this class of organometallic Ru(II) complexes as an antiproliferative agent.

Herein, novel ruthenium(II) complexes containing 1-methylimidazole as a ligand were obtained with the following formulas: [RuCl(1Meim)(dppb)(bpy)]Cl (1), [RuCl(1Meim)(dppb)(4,4′-DMbpy)]Cl (2), [RuCl(1Meim)(dppb)(5,5′-DMbpy)]Cl (3) and [RuCl(1Meim)(dppb)(phen)]Cl (4) where, 1Meim = 1-methylimidazole, dppb = 1,4-Bis(diphenylphosphino)butane, bpy = 2,2′-bipyridine, 4,4′-DMbpy = 4,4′-dimethyl-2,2′-bipyridine, 5,5′-DMbpy = 5,5′-dimethyl-2,2′-bipyridine and phen = 1,10-phenanthroline. Additionally, crystal structures containing the cations of (1) and (3) were obtained when the counter ion was exchanged, leading to the formation of [RuCl(1Meim)(dppb)(bpy)]PF6 (5) and [RuCl(1Meim)(dppb)(5,5′-DMbpy)]PF6 methanol solvate (6) where PF6 = hexafluorophosphate, showing one 1-methylimidazole molecule coordinated through the imidazole nitrogen, as expected. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV–Vis spectroscopy, 1H, 13C{1H} and 31P{1H} NMR, mass spectrometry and cyclic voltammetry. The interactions of complexes 1–4 with DNA and human serum albumin (HSA) were evaluated, and the cytotoxicity profiles of compounds 1–4 were determined using four different tumor cell lines derived from human cancers (melanoma: HT-144, colon: HCT-8, breast: MDA-MB-231 and lung: A549). A higher cytotoxic activity was observed for compound (3) against non-small cell lung cancer (A549). Complex (3) inhibited the clonogenic capacity and cell cycle progression of A549 cells and induced apoptosis involving mitochondrial pathway activation. Therefore, the data obtained in the present study support further investigations concerning molecular targets of complex (3) in non-small cell lung cancer.

In this study, Ru(II)-arene complexes with acylthiourea ligands of the type [Ru( η 6 ‑ p ‑cymene)(PPh 3 )(T)Cl]PF 6 ( 1 – 5 ) and [Ru( η 6 ‑ p ‑cymene)(PPh 3 )(T)]PF 6 ( 1a , 4a ), where PPh 3 = triphenylphosphine and T = N‑acyl‑N′(monosubstituted)thiourea, were synthesized and characterized, and their cytotoxic properties were also evaluated. 1a and 4a were obtained from the hydrolysis reaction of 1 and 4 . All complexes showed unusual coordination modes for acylthiourea ligands, which are coordinated in a monodentate fashion (S) in 1 – 5 , while they found to be bidentate (S,N), in 1a and 4a . To the best of our knowledge, 1a and 4a are the first crystallographically reported ruthenium compounds with acylthiourea coordinated via S and N(amide) atoms. The cytotoxicity of the compounds was evaluated in human lung cells, A549 and MRC-5. The IC 50 values ranging from 0.25 to 0.61 μM after 48 h incubation in lung cancer cells indicate that the compounds showed high cytotoxicity with values significantly lower than the reference drug, cisplatin (11.84 μM). Interaction studies were carried out using human serum albumin (HSA) and DNA. All complexes showed similar cytotoxic activity, however complex 1a , which is the hydrolysis product of 1 , presented the highest activity and selectivity among all seven compounds synthesized here. Complexes 1 and 1a inhibited the colony formation decreasing the colony size and inducing morphology changes in A549 cells. These complexes induced apoptosis cell death and promoted cell cycle arrest in the Sub-G1 phase with a decrease in the cell number at the S phase.

Made available in DSpace on 2018-12-11T17:26:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-01 Synthesis, characterization and anti-Mycobacterium tuberculosis assays of new platinum(II)/dppf/N,N-disubstituted-N′-acyl thiourea complexes with general formulae [Pt(dppf)(L)]PF6, [dppf = 1,1′-bis(diphenylphosphino)ferrocene; L = N,N-disubstituted-N′-acyl thioureas] is reported. The complexes were characterized by elemental analysis, molar conductivity, IR, NMR (1H, 13C and 31P{1H}) spectroscopy. The spectroscopic data are consistent with the complexes containing one dppf and one O, S chelated ligand. The crystal structures of complexes with N,N-diphenyl-N′-benzoylthiourea (L4), N,N-diethyl-N′-furoylthiourea (L5) and N,N-diphenyl-N′-(thiophene-2-carbonyl)thiourea (L8) were determined by X-ray crystallography, confirming the coordination of the ligands with the metal through sulfur and oxygen atoms, forming distorted square-planar structures. The complexes were screened with respect to their anti-M. tuberculosis activity (H37Rv ATCC 27294). Facultad de Química Universidad de la Habana Instituto de Física de São Carlos Universidade de São Paulo Departamento de Química Universidade Federal de São Carlos Faculdade de Ciências Farmacêuticas UNESP Faculdade de Ciências Farmacêuticas UNESP

This paper describes on the interaction studies of carbonyl heterobimetallic compounds of Ru(II)/Fe(II) containing polypyridyl ligands, with general formula ct–[RuCl(CO)(N–N)(dppf)]PF6, N–N = 1,10–phenanthroline (phen) 5; dipyrido[3,2–f:2′,3′–h]quinoxaline (dpq) 6; dipyrido[3,2–a:2′,3′–c]phenazine (dppz) 7; dipyrido[3,2–f:2′,3′–h]quinoxalino[2,3–b]quinoxaline (dpqQX) 8 and dppf = 1,1‘–bis(diphenylphosphino) ferrocene], with calf thymus DNA (ct–DNA) and bovine serum albumin (BSA). Also, it describes the cellular viability assays of these complexes in tumorigenic and non-tumorigenic cell lines. The carbonyl complexes 5–8 and their respective precursors with formula cis–[RuCl2(N–N)(dppf)], N–N = phen (1), dpq (2), dppz (3) and dpqQX (4), were characterized by elemental analysis and spectroscopic techniques (FTIR, UV–vis, 1H and 31P{1H} NMR). Also, a cyclic voltammetry study was performed for all complexes. The crystal structure of the complex 3 is presented and discussed. Spectrofluorimetric titrations shows spontaneous and strong interaction of 5–8 with BSA, through a static quenching mechanism, resulting in binding constants in the order of 104–106 L mol−1, at 310 K. Viscosity measurements and circular dichroism spectra prompts interactions of 5–8 with ct–DNA via non–classical intercalations or by an electrostatic pathway. MTT assays in breast tumor cells MDA–MB–231 and in non-tumorigenic cells MCF-10A and V79–4 cell lines revealed IC50 values ranging from 0.19 to 1.11 μmol L−1, 1.07–3.18 μmol L−1 and 1.29–3.85 μmol L−1 respectively, for complexes 5–8.

Organometallic ruthenium complexes as potential anticancer agents have been explored due to their suitable properties, such as stability in the solid state and in solution, water solubility and low toxicity. In this study, eight metal complexes of this class were synthesized, characterized and their important biological activities against a human breast tumor cell line (MDA-MB-231) were studied. Complexes 1-8 were obtained in good yields and have been characterized by satisfactory elemental analyses, IR, 1D and 2D 1H and 13C{1H} NMR, UV-Vis spectroscopy, cyclic voltammetry, ESI-MS and X-ray diffractometry (1, 2, 3 and 6). All complexes exhibit growth inhibition on human breast and lung tumor cell lines, with IC50 values ranging from 6.0 to 45.0 μM in 48 h. Four compounds were selected to evaluate the changes in the morphology, clonogenic, migration, cell cycle arrest and cell death in MDA-MB-231 cells. The complexes are able to induce morphological changes and inhibit the size, number of colonies and cell migration, and induce cell cycle arrest in the sub-G1 phase and apoptosis cell death. The interaction of the complexes with DNA was determined by performing spectroscopic titration, a competitive assay with thiazole orange, circular dichroism, gel electrophoresis and interactions with guanosine or guanosine monophosphate by 1H NMR, indicating the non-covalent interaction. The HSA binding affinity measured by spectrophotometric titration, revealed the hydrophobic and spontaneous association with the human protein. Overall, the studies indicated that these metal complexes are potential agents against MDA-MB-231 cells, encouraging us to continue studies of these types of compounds.

A series of copper(I)–phosphine polypyridyl complexes have been investigated as potential antitumor agents. The complexes [Cu(PPh3)2dpq]NO3 (2), [Cu(PPh3)2dppz]NO3 (3), [Cu(PPh3)2dppa]NO3 (4), and [Cu(PPh3)2dppme]NO3 (5) were synthesized by the reaction of [Cu(PPh3)2NO3] with the respective planar ligand under mild conditions. These copper complexes were fully characterized by elemental analysis, molar conductivity, FAB-MS, and NMR, UV–vis, and IR spectroscopies. Interactions between these copper(I)–phosphine polypyridyl complexes and DNA have been investigated using various spectroscopic techniques and analytical methods, such as UV–vis titrations, thermal denaturation, circular dichroism, viscosity measurements, gel electrophoresis, and competitive fluorescent intercalator displacement assays. The results of our studies suggest that these copper(I) complexes interact with DNA in an intercalative way. Furthermore, their high protein binding affinities toward human serum albumin were determined by fluores...

Made available in DSpace on 2018-12-11T17:36:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01. Added 1 bitstream(s) on 2019-10-09T18:33:12Z : No. of bitstreams: 1 S0103-50532018000601256.pdf: 1399196 bytes, checksum: 4adcb58edc86aa2a4ea4357033d86303 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) The syntheses, characterization, cytotoxicity against tumor cells and anti-Mycobacterium tuberculosis activity assays of PtII/PPh3/N,N-disubstituted-N’-acylthioureas complexes with general formulae [Pt(PPh3)2(L)]PF6, PPh3 = triphenylphosphine; L = N,N-disubstituted-N’-acylthiourea, are here reported. The complexes were characterized by elemental analysis, molar conductivity, infrared (IR), nuclear magnetic resonance (NMR) (1H, 13C{1H} and 31P{1H}) spectroscopy. The 31P{1H} NMR data are consistent with the presence of two PPh3 ligands cis to each other position, and one N,N-disubstituted-N’-acylthiourea coordinated to the metal through O and S, in a chelate form. The structures of the complexes were determined by X-ray crystallography, forming distorted square-planar structures. The complexes were tested in human cell lines carcinomas and also screened with respect to their anti-Mycobacterium tuberculosis activity (H37RvATCC 27294). It was found that complexes with N,N-disubstituted-N’-acylthiourea containing open and small chains as R2 groups show higher cytotoxic and higher anti-Mycobacterium tuberculosis activity than those containing rings in this position. Laboratorio de Síntesis Orgánica Facultad de Química Universidad de La Habana Instituto de Física de São Carlos Universidade de São Paulo Departamento de Química Universidade Federal de São Carlos Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (Unesp) Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (Unesp) CNPq: 2014/10516-7 CNPq: 2014/12566-1 CAPES: 339/2011 CAPES: CSS/CGCI/ 23038009487/2011-25/DRI/CAPES

Made available in DSpace on 2018-11-26T15:43:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-04-18 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Ruthenium complexes have been assessed as anti-tumor agents against cancer cells. In this project, new heteroleptic rutheniuM(II) complexes with general formulae [Ru(L)(bipy)(dppb)](PF6) (where L = N,N-disubstituted-N'-acylthiourea, bipy = 2,2'-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane) were synthesized and characterized by elemental analysis, IR and NMR and (H-1 and P-31{H-1}) spectroscopies, molar conductivity measurements and single crystal X-ray diffractometry. The IR and NMR data suggest the coordination of the ligands to the Ru(II) metal center through the tfiiocarbonyl and carbonyl groups. The structures of the new complexes were further studied by X-ray crystallography, which confirmed the coordination of the ligands with the metal through the sulfur and oxygen atoms, leading to the formation of distorted octahedral complexes. The N,N-disubstituted-N'-acylthioureas and their complexes were screened with respect to their in vitro cytotoxicity. All compounds exhibited considerable antipro-liferative activity against MCF-7 (human breast tumor cells ATCC HTB-26), DU-145 (human prostate tumor cells ATCC HTB-26), and relatively low toxicity against fibroblast L929 cells (health cell line from mouse ATCC CCL-1). A preliminary study regarding the mechanism of action of these compounds by con focal microscopy shows alterations of the actin filaments leading to Modifications in cytoskeletal supporting the cell death and that the cell nucleus is not main target of these complexes. (C) 2017 Elsevier Ltd. All rights reserved. Univ Fed Sao Carlos, Dept Quim, Sao Carlos, SP, Brazil Univ Fed Triangulo Mineiro, Dept Quim, BR-38025440 Uberaba, MG, Brazil Univ Estadual Paulista, Inst Biociencias, Campus Rio Claro, Sao Paulo, SP, Brazil Univ La Habana, Lab Sintesis Organ, Fac Quim, Havana, Cuba Univ Sao Paulo, Inst Quim Sao Carlos, Sao Carlos, SP, Brazil Univ Fed Sao Carlos, Dept Gerontol, Sao Carlos, SP, Brazil Univ Estadual Paulista, Inst Biociencias, Campus Rio Claro, Sao Paulo, SP, Brazil FAPESP: 2009/54011-8 FAPESP: 2011/16380-1 FAPESP: 2011/21033-9 FAPESP: 2013/21611-8

© Cambridge University Press 2016, We report the pharmacological activity of organoruthenium complexes containing chloroquine (CQ) as a chelating ligand. The complexes displayed intraerythrocytic activity against CQ-sensitive 3D7 and CQ-resistant W2 strains of Plasmodium falciparum, with potency and selectivity indexes similar to those of CQ. Complexes displayed activity against all intraerythrocytic stages, but moderate activity against Plasmodium berghei liver stages. However, unlike CQ, organoruthenium complexes impaired gametocyte viability and exhibited fast parasiticidal activity against trophozoites for P. falciparum. This functional property results from the ability of complexes to quickly induce oxidative stress. The parasitaemia of P. berghei-infected mice was reduced by treatment with the complex. Our findings demonstrated that using chloroquine for the synthesis of organoruthenium complexes retains potency and selectivity while leading to an increase in the spectrum of action and parasite killing rate relative to CQ., This research was funded by FAPESB (grant PET0042/2013, Brazil) to M.B.P.S, FAPESP (grant 14/10516-7, Brazil) to A.A.B. and Fundação para a Ciência e Tecnologia (grant PTDC/SAU-MIC/117060/2010 Portugal) to M.P. A.A.B. and M.B.P.S. are recipients of senior fellowships by CNPq (Brazil)