Investigating the antiproliferative activities of new CuII complexes with pyridine hydrazone derivatives of nalidixic acid.

To further explore the structural features and potential antibacterial and antitumor activities of polynuclear CuII coordination compounds with nalidixic acid (nx) derivatives, new complexes bearing nx hydrazones with N-pyridinyl moieties substituted at positions 2 and 3 (h2py and h3py) were synthesized. Complexes [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)]4BF4∙H2O (1), and [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)3]4BF4∙3H2O (%) (2) were synthesized using h2py and h3py with Cu(BF4)2∙nH2O as precursor, whereas the [Cu(C18H17N5O2)Cl2]∙0.5H2O complex (3) was synthesized with h2py and CuCl2∙2H2O. Crystallographic studies of complex 1, showed that coordination of hydrazones to CuII occurs by tridentate modes of type κ3(O,N,N') as well as bidentate modes of type κ2(O',N″). Complexes 1, 2 and 3 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by the determination of GI50 values. Complexes 1 and 2 were more active than complex 3, suggesting an effect of the complex charge on their activities. The interactions of such complexes towards bovine serum albumin (BSA) and DNA plasmid (pGEX-4 T1) were investigated using fluorescence spectroscopy and gel electrophoresis. All complexes were shown to interact with the DNA model as metallonucleases, but no interaction with BSA was observed. DNA molecular docking of complex 1 encompassing both its trinuclear (TN) form and a possible mononuclear (MN) derivative suggests that naphthyridyl ring performs π-stacking interactions with DNA. The TN species were also shown to be possible minor groove binders.

Complexos imínicos de cobre com atividade antiparasitária frente à doença de chagas / Imine copper complexes with antiparasitic activity against Chagas disease

Neste trabalho foram sintetizados e caracterizados três complexos de cobre com ligantes imínicos, com o objetivo de avaliar sua atividade tripanocida. Esses complexos foram caracterizados por diversas técnicas espectroscópicas, como UV-Vis, Infravermelho e EPR, além de análise elementar e espectrometria de massa. Juntamente com outros complexos similares previamente sintetizados pelo nosso grupo, tiveram suas atividades avaliadas frente à forma tripomastigota do parasita T. cruzi, responsável pela fase aguda da doença de Chagas, por ensaios de viabilidade celular, com determinação do valor de seus IC50, concentração em que observamos a morte de 50% da cultura celular, pela metodologia denominada MTT. Todos os complexos mostraram-se eficientes frente a tripomastigotas, apresentando valores de IC50 abaixo de 10 µM, com quatro deles obtendo índice de seletividade maior que 10, fator importante para definir agentes promissores antichagásicos. Complexos selecionados também tiveram sua atividade verificada frente à forma amastigota do parasita, responsável pela fase crônica da doença, utilizando método de imageamento por microscópio de fluorescência e contagem celular. Estudos de inibição da cruzaína, uma cisteíno-protease importante para o metabolismo do parasita foram conduzidos em colaboração com o laboratório do Prof. Wagner Alves de Souza Júdice, da Universidade de Mogi das Cruzes. Quatro dos compostos testados apresentaram atividade inibitória frente a cruzaína, sendo dois de cobre, um de zinco e um ligante livre. Os estudos também permitiram diferenciar os mecanismos de inibição dos compostos, com os complexos de cobre apresentando um mecanismo de inibição clássico e o composto de zinco e o ligante livre apresentando o mecanismo de inibição competitiva parabólica com cooperatividade

In this work, three copper complexes with iminic ligands were synthesized and characterized, with the objective of evaluating their trypanocidal activity. These complexes were characterized by several spectroscopic techniques, such as UV-Vis, Infrared and EPR, in addition to elementary analysis and mass spectrometry. Together with other similar complexes previously synthesized by our group, their activities were evaluated against the trypomastigote form of the parasite T. cruzi, responsible for the acute phase of Chagas disease, by cell viability tests, with determination of the value of their IC50, concentration in that we observed the death of 50% of the cell culture, by the methodology called MTT, all presenting IC50 values below 10 µM, with four of them obtaining a selectivity index greater than 10, important factor for defining promising antichagasic agents. Selected complexes also had their activity verified against the amastigote form of the parasite, responsible for the chronic phase of the disease, using a fluorescence microscope and cell counting imaging method. Inhibition studies of cruzain, a cysteine protease important for the metabolism of the parasite, were conducted in collaboration with the laboratory of Professor Wagner Alves de Souza Júdice at the University of Mogi das Cruzes. Four of the tested compounds showed inhibitory activity against cruzain, two of copper, one of zinc and a free ligand. The studies also allowed to differentiate the mechanisms of inhibition of the compounds, with the copper complexes presenting a classic inhibition mechanism and the zinc compound and the free ligand presenting the competitive parabolic inhibition mechanism with cooperativity

Abnormal co-doping effect on the red persistent luminescence SrS:Eu2+,RE3+ materials.

Persistent luminescence materials are a reality in several applications. However, there is still a lack of efficient red-emitting materials. SrS:Eu2+ phosphor is a potential candidate since its strong nephelauxetic effect shifts Eu2+4f65d1 → 4f7 to red, and its weak bond between strontium and sulphide, due to the soft base-hard acid character, generates a high number of intrinsic defects. SrS:Eu2+,RE3+ materials were efficiently prepared by two rounds of 22 min microwave-assisted solid-state synthesis. The highly crystalline purity and the material organization at the micro-scale were observed with X-ray powder diffraction and scanning electron microscopy, respectively. X-ray absorption spectroscopy revealed a low amount of Eu2+ compared to Eu3+ due to the efficient Eu2+ photo-oxidation by X-ray irradiation in the high storage capability SrS host matrix. Electron paramagnetic resonance spectra confirmed that at least 50% of Eu2+ ions in the material are photo-oxidized during excitation, reinforcing the previously established mechanisms. The RE2+ energy level positioned very close to or into the conduction band led to an abnormal co-doping effect, with similar effects independent of the co-dopant. The high concentration of intrinsic defects in SrS indicates that the soft-hard pair host is an excellent approach to develop efficient persistent luminescence materials.