Wendell Guerra

Two new ternary complexes of copper(II) with tetracycline or doxycycline and 1,10-phenanthroline and their potential as antitumoral: cytotoxicity and DNA cleavage.

This paper reports on the synthesis and characterization of two new ternary copper(II) complexes: [Cu(doxycycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (1) and [Cu(tetracycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (2). These compounds exhibit a distorted tetragonal geometry around copper, which is coordinated to two bidentate ligands, 1,10-phenanthroline and tetracycline or doxycyline, a water molecule, and a perchlorate ion weakly bonded in the axial positions. In both compounds, copper(II) binds to tetracyclines via the oxygen of the hydroxyl group and oxygen of the amide group at ring A and to 1,10-phenanthroline via its two heterocyclic nitrogens. We have evaluated the binding of the new complexes to DNA, their capacity to cleave it, their cytotoxic activity, and uptake in tumoral cells. The complexes bind to DNA preferentially by the major groove, and then cleave its strands by an oxidative mechanism involving the generation of ROS. The cleavage of DNA was inhibited by radical inhibitors and/or trappers such as superoxide dismutase, DMSO, and the copper(I) chelator bathocuproine. The enzyme T4 DNA ligase was not able to relegate the products of DNA cleavage, which indicates that the cleavage does not occur via a hydrolytic mechanism. Both complexes present an expressive plasmid DNA cleavage activity generating single- and double-strand breaks, under mild reaction conditions, and even in the absence of any additional oxidant or reducing agent. In the same experimental conditions, [Cu(phen)(2)](2+) is approximately 100-fold less active than our complexes. These complexes are among the most potent DNA cleavage agents reported so far. Both complexes inhibit the growth of K562 cells with the IC(50) values of 1.93 and 2.59 μmol L(-1) for compounds 1 and 2, respectively. The complexes are more active than the free ligands, and their cytotoxic activity correlates with intracellular copper concentration and the number of Cu-DNA adducts formed inside cells.

Tetraciclinas e glicilciclinas: uma visão geral

Tetracyclines exhibits activity to a broad range of Gram-negative and Gram-positive bacteria and this fact allied to the low toxicity, low cost, and the advantage of administration by oral route led to their indiscriminate use, which caused the appearance of bacterial resistance to these agents, wich has restricted its clinical utility, though new applications have emerged. On the other hand, the glycylcyclines, semi-synthetic products are similar to tetracyclines, which are active against many bacteria resistant to tetracycline and other classes of antibiotics. The purpose of this paper is to give an overview of this important class of antibiotics focusing on its coordination chemistry and possible applications.

Correlation between DNA interactions and cytotoxic activity of four new ternary compounds of copper(II) with N-donor heterocyclic ligands.

Four new ternary complexes of copper(II) were synthesized and characterized: [Cu(hyd)(bpy)(acn)(ClO4)](ClO4)] (1), [Cu(hyd)(phen)(acn)(ClO4)](ClO4)] (2), [Cu(Shyd)(bpy)(acn)(ClO4)](ClO4)] (3) and [Cu(Shyd)(phen)(acn)(ClO4)](ClO4)] (4), in which acn=acetonitrile; hyd=2-furoic acid hydrazide, bpy=2,2-bipyridine; phen=1,10-phenanthroline and Shyd=2-thiophenecarboxylic acid hydrazide. The cytotoxic activity of the complexes in a chronic myelogenous leukemia cell line was investigated. All complexes are able to enter cells and inhibit cellular growth in a concentration-dependent manner, with an activity higher than that of the corresponding free ligands. The substitution of Shyd for hyd increases the activity, while the substitution of bpy for phen renders the complex less active. Therefore, the most potent complex is 4 with an IC50 value of 1.5±0.2μM. The intracellular copper concentration needed to inhibit 50% of cell growth is approximately 7×10(-15)mol/cell. It is worth notifying that a correlation between cytotoxic activity, DNA binding affinity and DNA cleavage was found: 1<3<2<4.

Coordenação de metais a antibióticos como uma estratégia de combate à resistência bacteriana

Antibiotic resistance has been growing at an alarming rate and consequently the arsenal of effective antibiotics against Gram-negative and Gram-positive bacteria has dropped dramatically. In this sense there is a strong need to produce new substances that not only have good spectrum of activity, but having new mechanisms of action. In this regard, this paper emphasizes the coordination of metals to antibiotics as a strategy for reversing antibiotic resistance and production of new drugs, with a special focus on quinolones, fluoroquinolones, sulfonamides and tetracyclines.

Three New Complexes of Platinum(II) with Doxycycline, Oxytetracycline and Chlortetracycline and their Antimicrobial Activity

Este artigo descreve a sintese e a caracterizacao de tres novos complexos de platina(II) com a oxitetraciclina, doxiciclina e clortetraciclina por analise elementar, espectroscopias IV e RMN de 195Pt. As interacoes da doxiciclina com ions PtII em funcao do pH foram estudadas por RMN de 1H. Todas as tetraciclinas investigadas formam complexos 1:1 com a PtII via oxigenio do grupo hidroxila e oxigenio do grupo amida do anel A. As concentracoes minimas inibitorias (MIC) dos ligantes e de seus complexos de PtII foram determinadas em duas cepas sensiveis (E. coli HB 101 and E. coli ATCC 25922) e em uma resistente (E. coli HB101/pBR322). O complexo de platina da doxiciclina e duas vezes mais potente do que o antibiotico livre na cepa resistente. Os coeficientes de particao dos complexos em octanol e agua foram determinados. O aumento da lipofilia causa um aumento da atividade antimicrobiana na cepa resistente.

Cytotoxicity and Cellular Accumulation of Palladium(II) Complexes of Tetracyclines

We studied the cytotoxic effect and the uptake of PdII complexes of doxycycline (Dox), [Pd(Dox)Cl2] (1), and tetracycline (Tc), [Pd(Tc)Cl2] (2), in chronic myelogenous leukemia cells. The effect of the compounds on macrophage viability was also investigated. Compound 1 is more effective than compound 2 in inhibiting the growth of K562 cells with the IC50 values of 14.44 and 34.54 μM, respectively. There is a good correlation between cell‐growth inhibition and intracellular metal concentrations, determined by inductively coupled plasma atomic emission spectroscopy (ICP‐AES). Incubation of the cells with equitoxic concentrations of both compounds yields approximately the same intracellular Pd concentration. At the IC50 doses, intracellular concentration is ca. 33×10−16 mol/cell for both compounds 1 and 2. This suggests that more [Pd(Tc)Cl2] is needed to produce a cytotoxic effect, because it enters cells more slowly. Both compounds up to 16 μM did not affect the viability of mouse peritoneal macrophages after a 48‐h incubation. After 72 h of incubation, the IC50 values are 22 for [Pd(Dox)Cl2] and 40 μM for [Pd(Tc)Cl2]. Therefore, the cytotoxic effect in cancer cells exhibited by both compounds is higher than their effect in macrophages.

Síntese e caracterização de novos complexos de platina (II) com ligantes derivados do furano e nitrofurano

Platinum (II) complexes, for example, cisplatin and carboplatin, have been used as chemotherapeutic agents for the treatment of various types of cancer. Several other complexes of this metallic ion are also under clinical evaluation. This work describes the synthesis of five new platinum (II) complexes having furan and 5-nitrofuran derivatives and chloride as ligands. The compounds were characterized by NMR, IR and elemental analysis.

SÍNTESE E CARACTERIZAÇÃO DE UM NOVO COMPLEXO DE PLATINA (IV) A PARTIR DE SEU ANÁLOGO DE PLATINA (II) UTILIZANDO IODO MOLECULAR COMO AGENTE OXIDANTE: UMA ROTA SINTÉTICA INTERESSANTE PARA OBTENÇÃO DE NOVOS COMPLEXOS DE PLATINA

In an attempt to reduce toxicity and widen the spectrum of activity of cisplatin and its analogues, much attention has been focused on designing new platinum complexes. This work reports the synthesis and characterization of novel compounds of the platinum (II) and platinum (IV) containing 2-furoic hydrazide acid and iodide as ligands. Although the prepared compounds do not present the classical structure of biologically active platinum analogues, they could be potentially active or useful as precursors to prepare antitumor platinum complexes. The reported compounds were characterized by 1H NMR, 13C NMR, 195Pt NMR, IR and elemental analyses.

Síntese e caracterização de complexos de platina (II) contendo iodeto e derivados do furano como ligantes

Platinum (II) compounds, for example, cisplatin, carboplatin and oxaloplatin, have been used as chemotherapeutic agents for the treatment of various types of cancer. However, in an attempt to reduce toxicity and widen the spectrum of activity of cisplatin and its analogous, thousands of platinum complexes have been prepared by varying the nature of the leaving groups and the carrier ligands. This work reports the synthesis and characterization of novel structural types of the platinum compounds, having iodide and furan derivatives as ligands. The compounds were characterized using NMR, IR and elemental analysis.

Prata: Breve histórico, propriedades e aplicações

Silver: Brief history, properties and applications Silver, a malleable metal, ductile, bright, known since prehistoric times is widely used in photographic industry, of jewelry and decorative objects. Due to its remarkable physical and chemical properties, new applications have emerged. Considering the importance of this element, this article describes their history, properties and applications.