Abstract Chemotherapy stands out as the main systemic treatment strategy against cancer and still faces problems related to multidrug resistance and severe side effects. Copper-based drugs have been widely explored in medicinal chemistry, since copper is an essential metal for physiological activities with antineoplastic effects. In this context, the present study aimed to evaluate the recombinogenic/mutagenic and anticarcinogenic potential of the complex CBP-01 - [Cu(bta)(1,10-phen)ClO4] (Hbta = 4,4,4-trifluoro-1-phenyl-1,3-butanedione and 1,10-phen =1,10-phenanthroline) - through the Somatic and Recombination test (SMART) and the Epithelial Tumor Test (ETT) in Drosophila melanogaster, compared with carboplatin (CARB) and cisplatin (CIS) effects. According to our results, CARB and CIS induced a high frequency of mutant spots, which was not verified at higher concentrations of CBP-01. In addition, CBP-01 exhibited mutagenic/recombinogenic potential only at the lowest concentration and after biometabolization. Subsequently, in the ETT test, CBP-01 did not demonstrate carcinogenic effect. Lastly, epithelial tumors were identified in flies treated with CARB and CIS, which were modulated by the CBP-01 complex. Therefore, CBP-01 modulates genotoxicity of other compounds and is a promising metal-based drug for the development of a new anticancer agent or for optimization of therapeutic regimens. effects Copperbased Copper based chemistry context recombinogenicmutagenic recombinogenic mutagenic CBP01 CBP 01 CBP-0 Cubta1,10phenClO4 Cubta110phenClO4 CubtaphenClO Cu bta 1,10 phen ClO4 1 10 ClO [Cu(bta)(1,10-phen)ClO4 Hbta 4,4,4trifluoro1phenyl1,3butanedione 444trifluoro1phenyl13butanedione trifluorophenylbutanedione 4,4,4 trifluoro phenyl 1,3 butanedione 4 3 1,10phen 110phen =1,10phenanthroline 110phenanthroline phenanthroline =1,10 =1,10-phenanthroline SMART (SMART (ETT melanogaster (CARB (CIS results spots CBP01. 01. addition mutagenicrecombinogenic biometabolization Subsequently effect Lastly Therefore metalbased regimens CBP0 0 CBP- Cubta1 10phenClO4 Cubta phenClO Cubta1,10phenClO Cubta110phenClO 110 1,1 [Cu(bta)(1,10-phen)ClO 4trifluoro1phenyl1 3butanedione 444 4,4, 13 1, 10phen 10phenanthroline =1,1 10phenClO 11 trifluorophenyl 4trifluoro1phenyl 44 4,4 =1, 4, =1

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.

Plata, un metal maleable, dúctil, brillante, conocido desde tiempos prehistóricos y muy utilizado em la industria fotográfica, de joyería y objetos de decoración. Debido a sus notables propiedades físico-químicas, han surgido nuevas aplicaciones. Considerando la importancia de este elemento, este artículo describe su historia, propiedades y aplicaciones.

Tantalum, a malleable metal, ductile, of high melting point, is mainly used to obtain special alloys, capacitors, and plates for skull fractures repairing, among other applications. Considering the importance of this element, in this article we describe its history, properties and applications.

Tántalo, un metal maleable, dúctil, de alto punto de fusión, es utilizado primordialmente en la obtención de aleaciones especiales, capacitores, placas para reparar fracturas de cráneo, entre otras cuestiones. Al considerar la importancia de este elemento describimos aquí su historia, propiedades y aplicaciones.

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.

Este artigo descreve a síntese e caracterização de um novo complexo binuclear de paládio (II) contendo o antibiótico oxitetraciclina. O complexo foi caracterizado pelas técnicas usuais de análise. Pela análise do espectro de infravermelho sugerimos que o íon paládio(II) coordena-se no anel A, mais especificamente nos oxigênios da amida e da hidroxila vizinha no anel A e aos oxigênios da carbonila em C11 e da hidroxila em C12.

This article reports the synthesis and characterization of a new binuclear complex of palladium (II) containing the antibiotic oxytetracycline. The complex was characterized by the usual techniques of analysis. With respect to sites of coordination, the IR spectral data suggests the involvement the oxygen of the amide group and the oxygen of the neighbor hydroxyl group at ring A and to the carbonyl oxygen at C11 and the hydroxyl group at C12.

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.

As propriedades antitumorais de complexos de PtII e as características favoráveis das tetraciclinas levaram-nos a estudar compostos de PtII da tetraciclina (tc) e doxiciclina (dox) como candidatos a agentes antitumorais. [PtCl2(dox)], 1, é mais potente que[PtCl2(tc)], 2,em inibir o crescimento de células de leucemia mielóide crônica.Os compostos 1 e 2 formam um complexo ternário com o ADN com valores de K iguais a 3,85×10(4) e 5,43×10(4), respectivamente. Os complexos deslocam o brometo de etídeo dos sítios no ADN, o que indica um mecanismo intercalativo. Ambos os complexos diminuem a mobilidade eletroforética e a temperatura de fusão do ADN. Após a incubação das células com 1 e 2, o ADN foi extraído e os adutos formados foram quantificados. Na concentração em que os compostos são citotóxicos contra células cancerosas, eles não afetam a viabilidade de macrófagos. A velocidade de entrada do complexo da doxiciclina nas células é três vezes maior do que a do complexo da tetraciclina e isto parece ser determinante para a sua maior atividade.

The antitumoral properties of PtII compounds and the favorable characteristics of tetracyclines led us to study PtII compounds of tetracycline (tc) and doxycycline (dox) as candidates for anticancer agents. [PtCl2(dox)], 1, is more potent than [PtCl2(tc)], 2, in inhibiting the growth of chronic myelogenous leukemia cells. Compounds 1 and 2 form a ternary complex with DNA withK values of 3.85×10(4) and 5.43×10(4), respectively. The compounds displace ethidium bromide from DNA sites, which points to an intercalative mechanism. Both complexes decrease DNA eletrophoretic mobility and melting temperature. After incubation of cells with 1 and 2, the DNA was extracted and the adducts formed were quantified. At the concentration that the compounds are cytotoxic to cancer cells, they do not affect macrophages viability. The rate of uptake of the doxycycline complex in cells is three times higher than that of the tetracycline complex and this seems to be determinant for its higher activity.

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.

Este artigo descreve a síntese e a caracterização de três novos complexos de platina(II) com a oxitetraciclina, doxiciclina e clortetraciclina por análise elementar, espectroscopias IV e RMN de 195Pt. As interações da doxiciclina com íons PtII em função do pH foram estudadas por RMN de ¹H. Todas as tetraciclinas investigadas formam complexos 1:1 com a PtII via oxigênio do grupo hidroxila e oxigênio do grupo amida do anel A. As concentrações mínimas inibitórias (MIC) dos ligantes e de seus complexos de PtII foram determinadas em duas cepas sensíveis (E. coli HB 101 and E. coli ATCC 25922) e em uma resistente (E. coli HB101/pBR322). O complexo de platina da doxiciclina é duas vezes mais potente do que o antibiótico livre na cepa resistente. Os coeficientes de partição dos complexos em octanol e água foram determinados. O aumento da lipofilia causa um aumento da atividade antimicrobiana na cepa resistente.

This paper reports on the synthesis and characterization of three new platinum(II) complexes with oxytetracycline, doxycycline and chlortetracycline by elemental analysis, IR and 195Pt RMN spectroscopies. Doxycycline interactions with PtII ions as a function of the pH were studied by ¹H NMR. All the investigated tetracyclines form 1:1 complexes with PtII via the oxygen of the hydroxyl group and oxygen of the amide group at ring A. The minimal inhibitory concentrations (MIC) of the ligands and those of their PtII compounds were determined in two sensitive strains (E. coli HB 101 and E. coli ATCC 25922) and in a resistant one (E. coli HB101/pBR322). Platinum complex of doxycycline is twice as potent as the free antibiotic in the resistant strain. Octanol/water partition coefficients of the complexes were determined. Increasing lipophilicity enhances antimicrobial activity in the resistant strain.

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.