Navegando por Autor "Graminha, Angelica Ellen"
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Item Anti-mycobacterium tuberculosis and cytotoxicity activities of Ruthenium(II)/ bipyridine/diphosphine/pyrimidine-2-thiolate complexes : the role of the non- coordinated N-atom.(2016) Benedicto, Augusto Vieira Lima; Correa, Rodrigo de Souza; Graminha, Angelica Ellen; Kuznetsov, Aleksey Evgenyevich; Ellena, Javier Alcides; Pavan, Fernando Rogério; Leite, Clarice Queico Fujimura; Batista, Alzir AzevedoThe [Ru(Spym)(bipy)(P–P)]PF6, [Spym = pyrimidine-2-thiolate anion; P–P = 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane and 1,1’-bis(diphenylphosphino)ferrocene] complexes were synthesized and characterized by spectroscopic, electrochemical and elemental analysis, and by X-ray crystallography. The minimal inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis and the complex concentration causing 50% tumor cell growth inhibition (IC50) against breast cancer cells, MDA-MB-231, were determined. All three compounds gave promising values in both tests. It is interesting to mention that all three complexes display MICs against Mycobacterium tuberculosis showing higher activity than cycloserine, a second line drug used in the treatment of the illness. The complexes interact weakly with the DNA.Item Antitumor and anti-Mycobacterium tuberculosis agents based on cationic ruthenium complexes with amino acids.(2017) Santos, Edjane Rocha dos; Correa, Rodrigo de Souza; Cunha, Lucas Vinícius Pozzi da; Graminha, Angelica Ellen; Araujo, Heloisa Sobreiro Selistre de; Pavan, Fernando Rogério; Batista, Alzir AzevedoSix new complexes of Ru(II)/phenanthroline/1,4-bis(diphenylphosphino)butane containing amino acids (Glycine, L-Alanine, L-Valine, L-Tyrosine, L-Methionine or L-Tryptophan) were synthesized and characterized by IR, 31P{1H}, 13C and 1H NMR spectroscopies and cyclic voltammetry experiments. These data suggest the presence of diastereoisomers, except for the complex with glycine, amino acid that does not exhibit chiral carbon. The compounds are active against the MDA-MB-231 tumor cells and against Mycobacterium tuberculosis. The cationic ruthenium complexes with amino acids, reported here, show similar cytotoxicity against the MDA-MB-231 tumor cells. When compared with analogs complexes containing 2,20-bipyridine as ligands, instead of 1,10-phenatroline, the new complexes studied here are, in general, roughly twice more active than the 2,20-bipyridine ones and their IC50 values comparable with the cisplatin. In addition, low MICs values were obtained against Mycobacterium tuberculosis compared with the reference drugs, cycloserine and ethambutol.Item Cytotoxic activity and structural features of Ru(II)/phosphine/amino acid complexes.(2018) Santos, Edjane Rocha dos; Graminha, Angelica Ellen; Schultz, Mario Sergio; Correia, Isabel; Araujo, Heloisa Sobreiro Selistre de; Correa, Rodrigo de Souza; Ellena, Javier Alcides; Lacerda, Elisângela de Paula Silveira; Pessoa, João Costa; Batista, Alzir AzevedoThirteen new ruthenium amino acid complexes were synthesized and characterized. They were obtained by the reaction of α-amino acids (AA) with [RuCl2(P-P)(N-N)], where P-P = 1,4-bis(diphenylphosphino)butane (dppb) or 1,3-bis(diphenylphosphino)propane (dppp) and N-N = 4,4′-dimethyl-2,2′-bipyridine (4′-Mebipy), 5,5′-dimethyl-2,2′-bipyridine (5′-Mebipy) or 4,4′-Methoxy-2-2′-bipyridine (4′-MeObipy). This afforded a family of complexes formulated as [Ru(AA-H)(P-P)(N-N)]PF6, where AA = glycine (Gly), L-alanine (Ala), L-valine (Val), L-tyrosine (Tyr), L-tryptophan (Trp), L-histidine (His) and L-methionine (Met). All compounds were characterized by elemental analysis, spectroscopic and electrochemical techniques. The [Ru(AA-H)(P-P)(N-N)]PF6 complexes are octahedral (the AA-H ligand binding involves N-amine and O-carboxylate), diamagnetic (low-spin d6, S = 0) and present bands due to electronic transitions in the visible region. 1H, 13C{1H} and 31P{1H} NMR spectra of the complexes indicate the presence of C2 symmetry, and the identification of diastereoisomers. In vitro cytotoxicity assays of the compounds and cisplatin were carried out using MDA-MB-231 (human breast) tumor cell line and a non-tumor breast cell line (MCF-10A). Most complexes present promising results with IC50 values comparable with the reference drug cisplatin and high selectivity indexes were found for the complexes containing L-Trp. The binding of two Ru-precursors of the type [RuCl2(dppb)(NN)] (N-N = 4′-MeObipy or 4′-Mebipy) to the blood transporter protein human serum albumin (HSA) was evaluated by fluorescence and circular dichroism spectroscopy. Both complexes bind HSA, probably in the hydrophobic pocket near Trp214, and the Ru-complex containing 4′-MeObipy shows higher affinity for HSA than the 4′-Mebipy one.Item New heteroleptic RuII/diphosphine complexes with cytotoxicity against human breast and murine ascitic sarcoma 180 tumor cells.(2020) Lima, Benedicto Augusto Vieira; Correa, Rodrigo de Souza; Graminha, Angelica Ellen; Varela Júnior, Jaldyr de Jesus Gomes; Silva, Albérico Borges Ferreira da; Ellena, Javier Alcides; Silva, Thales E. M.; Batista, Alzir AzevedoThe preparation, characterization, theoretical calculations and biological application of four RuII complexes with 2-picolinate (pic), 2,2’-bipyridine (bipy) and P-P as ligands [P-P = 1,1-bis(diphenylphosphino)methane (dppm-1), 1,2-bis(diphenylphosphino)ethane (dppe-2), 1,3-bis(diphenylphosphino)propane (dppp-3) or 1,1’-bis(diphenylphosphino)ferrocene (dppf-4)], is here presented. The complexes 1-4, with general formula [Ru(pic)(P-P)(bipy)]PF6, were characterized by elemental analysis and by infrared (IR), UV-Vis, nuclear magnetic resonance (NMR 1 H and 13P{1 H}) spectroscopies, cyclic voltammetry and X-ray crystallography technique. Additionally, preliminary in vitro tests against human breast (MDA-MB-231) and murine ascitic sarcoma 180 (S180) tumor cell lines were carried out, and compared with cisplatin, a reference drug. The drug concentration at which 50% of the cells are viable relative to the control (IC50) values found for complexes 1, 2, 3 and 4 against MDA-MB-231 tumor cells were around 14.6, 7.6, 3.3 and 0.4 μM, respectively, while against S180 tumor cells these complexes showed IC50 values of 71.9, 31.3, 11.2 and 3.5 μM, respectively. Therefore, the complexes were more active against MDA-MB-231 than S180.Item New ruthenium complexes containing salicylic acid and derivatives induce triple-negative tumor cell death via the intrinsic apoptotic pathway.(2022) Graminha, Angelica Ellen; Popolin, Cecília; Araujo Neto, João Honorato de; Correa, Rodrigo de Souza; Oliveira, Katia Mara de; Godoy, Luani Rezende; Colina Vegas, Legna Andreina; Ellena, Javier Alcides; Batista, Alzir Azevedo; Cominetti, Márcia ReginaIn this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF6 and [Ru(L)(dppe)2]PF6 where L = salicylic acid (Sal), 4-aminosalicylic acid (AmSal) or 2,4-dihydroxybenzoic acid (DiSal), dppb = 1,4-bis(diphenylphosphino)butane, dppe = 1,2-bis (diphenylphosphino)ethane and bipy = 2,2′ -bipyridine. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR, UV–vis and IR spectroscopies, and two by X-ray crystallography. The 31P{1 H} NMR spectra of the complexes with the general formula [Ru(L)(dppe)2]PF6 showed that the phosphorus signals are solvent-dependent. Aprotic solvents, which form strong hydrogen bonds with the complexes, inhibit the free rotation of the salicylic acid-based, modifying the diphosphine cone angles, leading to distortion of the phosphorus signals in the NMR spectra. The cytotoxicity of the complexes was evaluated in MCF7, MDA-MB-231, SKBR3 human breast tumor cells, and MCF-10 non-tumor cell lines. The complexes with the structural formula [Ru(L)(dppe)2]PF6 were the most cytotoxic, and the complex [Ru(AmSal)(dppe)2]PF6 with L = 4-aminosalicylic acid ligand was the most selective for the MDA-MB-231 cell line. This complex interacts with the transferrin and induces apoptosis through the intrinsic pathway, as demonstrated by increased levels of proteins involved in apoptotic cell death.Item A novel ruthenium(II) gallic acid complex disrupts the actin cytoskeleton and inhibits migration, invasion and adhesion of triple negative breast tumor cells.(2021) Graminha, Angelica Ellen; Araujo Neto, João Honorato de; Correa, Rodrigo de Souza; Cominetti, Márcia Regina; Menezes, Antônio Carlos Severo; Batista, Alzir AzevedoThis work describes the synthesis of three new ruthenium(II) complexes with gallic acid and derivatives of the general formula [Ru(L)(dppb)(bipy)]PF6, where L = gallate (GAC), benzoate (BAC), and esterified-gallate (EGA), bipy = 2,2’-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane. The complexes were characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis and IR spectroscopy, and two of them by X-ray crystallography. Cell viability assays show promising results, indicating higher cytotoxicity of the complexes in MDA-MB-231 cells, a triple-negative breast cancer (TNBC) cell line, compared with the hormone-dependent MCF-7 cell line. Studies in vitro with the MDA-MB-231 cell line showed that only Ru(BAC) and Ru(GAC) interacted with BSA. Besides that, the Ru(GAC) complex, which has a polyphenolic acid, interacted in an apo-Tf structure and function dependent manner and it was able to inhibit the formation of reactive oxygen species. Ru(GAC) was able to cause damage to the cellular cytoskeleton leading to inhibition of some cellular processes of TNBC cells, such as invasion, migration, and adhesion.Item Ruthenium(II) complexes of 1,3-thiazolidine-2-thione : cytotoxicity against tumor cells and anti-Trypanosoma cruzi activity enhanced upon combination with benznidazole(2016) Correa, Rodrigo de Souza; Silva, Monize Martins da; Graminha, Angelica Ellen; Meira, Cássio Santana; Santos, Jamyle Andrade Ferreira dos; Moreira, Diogo Rodrigo de Magalhães; Soares, Milena Botelho Pereira; Poelhsitz, Gustavo Von; Castellano, Eduardo Ernesto; Bloch Junior, Carlos; Cominetti, Márcia Regina; Batista, Alzir AzevedoThree newmixed and mononuclear Ru(II) complexes containing 1,3-thiazolidine-2-thione (tzdtH) were synthesized and characterized by spectroscopic analysis, molar conductivity, cyclic voltammetry, high-resolution electrospray ionization mass spectra and X-ray diffraction. The complexes presented unique stereochemistry and the proposed formulae are: [Ru(tzdt)(bipy)(dppb)]PF6 (1), cis-[Ru(tzdt)2(PPh3)2] (2) and trans- [Ru(tzdt)(PPh3)2(bipy)]PF6 (3), where dppb = 1,4-bis(diphenylphosphino)butane and bipy= 2,2′-bipyridine. These complexes demonstrated strong cytotoxicity against cancer cell lines when compared to cisplatin. Specifically, complex 2 was the most potent cytotoxic agent against MCF-7 breast cells, while complexes 1 and 3 were more active in DU-145 prostate cells. Binding of complexes to ctDNA was determined by UV–vis titration and viscosity measurements and revealed binding constant (Kb) values in range of 1.0–4.9 × 103 M−1, which are characteristic of compounds possessing weak affinity to ctDNA. In addition, these complexes presented antiparasitic activity against Trypanosoma cruzi. Specifically, complex 3 demonstrated strong potency, moderate selectivity index and acted in synergism with the approved antiparasitic drug, benznidazole. Additionally, complex 3 caused parasite cell death through a necrotic process. In conclusion, we demonstrated that Ru(II) complexes have powerful pharmacological activity, while the metal-free tzdtH does not provoke the same outcome.