Síntese e estudos espectroscópicos de organometálicos de rutênio-areno contendo fármacos anti-inflamatórios e derivados como ligantes / Synthesis and spectroscopic studies of ruthenium-arene organometallics bearing anti-inflammatory drugs and derivatives as ligands

Compostos organometálicos do tipo rutênio-areno têm sido estudados no transcurso dos últimos anos em razão do potencial que apresentam para o tratamento de doenças dentre as quais se destaca o câncer. Neste contexto, o presente trabalho teve como principal objetivo o estudo de organometálicos de Ru(II)-p-cimeno contendo como ligantes fármacos anti-inflamatórios não esteroides (FAINEs) ou seus derivados piridinaamida (FAINE-amida). Foram realizadas as sínteses de duas classes de compostos de fórmulas gerais [RuCl(p-cimeno)L] e [RuCl2(p-cimeno)Lam] em que L = ibuprofeno, naproxeno ou indometacina e Lam = derivado amida desses FAINES, respectivamente. A composição e estrutura dos compostos foram elucidadas principalmente com base em análise elementar, espectrometria de massas (ESI-MS), espectroscopia de ressonância magnética nuclear (1H RMN, 13C RMN, HSQC, HMBC) e espectroscopia vibracional ATR/FT-IR. Os dados indicaram que todos os fármacos-ligantes utilizados estabilizam a unidade Ru(II)-areno, sendo que os carboxilatos coordenam-se ao Ru(II) de modo bidentado por ambos os átomos de oxigênio, enquanto que a coordenação dos derivados amida ocorre pelo nitrogênio do anel piridínico. No entanto, em contraste ao comportamento em solventes não-coordenantes como clorofórmio, estudos em solução indicaram que a presença de dimetilsulfóxido promove dissociação do fármaco ligante acompanhada pela coordenação do solvente (gradual, no caso de L, ou imediata total no caso de Lam). Resultados preliminares de estudos de espectroscopia de fluorescência sugerem interação dos compostos de Ru(II)-areno-indometacina com albumina de soro humano (HSA)

Ruthenium-arene organometallics have been investigated in recent years due to the potential for treatment of diseases among which cancer is highlighted. In this context, the main objective of the present work is the study of organometallics of Ru(II)-p-cymene bearing non steroidal anti-inflammatory drugs (NSAIDs) or their pyridine-amide (NSAIDamide) as ligands. Two classes of compounds of general formula [RuCl(p-cymene)L] and [RuCl2(p-cymene)Lam], in which L = ibuprofen, naproxen or indomethacin and Lam = amide derivative of these NSAIDs, respectively have been synthesized. The composition and the structure of these compounds have been elucidated mainly based on elemental analysis, mass spectrometry (ESI-MS), nuclear magnetic resonance spectroscopy (1H RMN, 13C RMN, HSQC, HMBC) and vibrational spectroscopy (ATR/FT-IR). The data indicate that all the used drug-ligands stabilize the Ru(II)-arene framework, being that the carboxylates coordinate Ru(II) in bidentate mode through both oxygen atoms while the coordination of the amide derivatives occurs via nitrogen atom of the pyridine ring. However, in contrast to the behavior in non-coordinating solvents such as chloroform, studies in solution indicate that the presence of dimethylsulfoxide promotes dissociation of the drug ligand accompanied by the coordination of the solvent (gradual, for L, or total immediate for Lam). Preliminary results from fluorescence spectroscopy suggest interaction of the Ru(II)-arene-indomethacin compounds with human serum albumin (HSA)

Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites

This work reports the in vitro activity against Plasmodium falciparumblood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.

Production, quality control and biological evaluation of [153] Sm-TTHMP as a possible bone palliation agent

Various bone palliative therapeutic agents have been developed and widely used for bone metastasis such as [153]Sm-EDTMP. In this study, production, quality control and biodistribution studies of a newly developed therapeutic compound have been presented followed by imaging studies in wild-type rodents. [153]Sm-TTHMP was prepared starting from [153]Sm-SmCl[3], prepared by neutron activation of an enriched [152]Sm sample [purity >98%], and in-house synthesized TTHMP in 1h at 25[degree sign] C followed by stability tests, partition coefficient determination and biodistribution studies of in wild-type rodents using scarification and SPECT imaging. The radiolabled Sm complex was prepared in high radiochemical purity [>99%, ITLC] and specific activity of 278 GBq/mmol and demonstrated significant ability at 4, 25 and 37 [degree sign] C [in presence of human serum]. Initial biodistribution data showed significant bone accumulation of the tracer in 48h. [153]Sm-TTHMP can be a potential candidate for bone pain palliation therapy in skeletal metastases, although further biological studies in other mammals is still needed

Atividade moluscicida da mistura de ácidos 6-n-alquil salicílicos (ácido anacárdico) e dos seus complexos com cobre (II) e chumbo (II) / Molluscacide activity of a mixture of 6-n-alkyl salicylic acids (anardic acid) and 2 of its complexes with copper (II) and lead (II)

Foi comparada, em laboratório, a atividade moluscicida do extrato hexânico da casca da castanha do caju - Anacardium occidentale L. (EHCCC), do complexo de cobre (II), do complexo de chumbo (II) e do ácido anacárdico com objetivo de encontrar entre eles um produto que apresentasse maior estabilidade que o ácido anacárdico. Este foi preparado tratando o EHCCC com hidróxido de chumbo (II) ou com o sulfato de cobre mais hidróxido de sódio ou com hidróxido de cobre (II). Em seguida, o complexo de chumbo (II) ou os complexos de cobre(II) preprarados foram tratados com uma soluçäo de ácido sulfúrico diluída. As misturas dos dez produtos obtidos foram testadas sobre caramujos adultos de Biomphalaria galabrata nas concentraçöes de 1 a 10 ppm. Os mais ativos foram o compleso de cobre (II), obtido com sulfato de cobre mais hidróxido de sódio, e o ácido anacárdico (hidróxido de chumbo) que apresentaram atividade a partir da concentraçäo de 4ppm. O teor de chumbo do ácido anacárdico (hidróxido de chumbo) foi acima das normas recomendadas pelos Padröes de Saúde Pública dos Estados Unidos

Selective cleavage of N-terminal amino acid in a peptide by polymeric cobalt (III) triene complex.

Cellulose was functionalized to incorporate triethylenetetramine group. This was in turn converted into the polymeric analogue of cobalt(III)triene complex. The polymeric complex reacts with peptides resulting in the cleavage of amino end amino acid, thus suggesting the applicability of the polymeric reagent as a solid phase reagent for N-terminal determination.