MODELO INTERTEMPORAL DA CONTA CORRENTE: EVIDÊNCIAS PARA O BRASIL

The paper uses the procedure developed first by Campbell (1987) to test, for the Brazilian economy, the proposition that the balance of the current account is negatively related to the present value of the future changes of the GDP net of the investment and consumption of the government. Within the framework of intertemporal choice transitory shocks should affect the current account since the agents use credit or give loans in the international capital market to smooth the consumption pattern. On the contrary, when the shocks are permanent the agents adjust to a new consumption level and the effect on the current account is small. This means that the model should adjusts fairly well in countries with short run fluctuations. The empirical results of this work suggest that the present value of the future GDP path is able to explain the behavior of the quarter and annual Brazilian current account giving support to the model of intertemporal choice optimization.

Elucidating the chemiexcitation of dioxetanones by replacing the peroxide bond with S-S, N-N and C-C bonds

Dioxetanone is one of the prototypical cyclic peroxide intermediates in several chemiluminescent and bioluminescent systems, in which thermolysis reactions allow efficient singlet chemiexcitation. While the chemiexcitation mechanism of dioxetanone and peroxide intermediates is still far from understood, the presence of a peroxide bond that undergoes bond breaking has been found to be a constant. Here we have addressed the following questions: can other non-peroxide bonds lead to chemiexcitation and, if not, can the differences between dioxetanone and non-peroxide derivatives help to elucidate their chemiexcitation mechanism? To this end, we have used a reliable TD-DFT approach to model the thermolysis and chemiexcitation of a model dioxetanone and its three other non-peroxide derivatives. The results showed that only the dioxetanone molecule could lead to chemiluminescence as it is the only one for which thermolysis is energetically favorable and provides a pathway for singlet chemiexcitation. Finally, the chemiexcitation of the model dioxetanone is explained by its access, during thermolysis, to a biradical region where the ground and excited states are degenerate. This occurs due to an increased interaction between the reaction fragments, which extends the biradical regions and delays the rupture of the peroxide ring

Combined Experimental and Theoretical Investigation into the Photophysical Properties of Halogenated Coelenteramide Analogs

Marine Coelenterazine is one of the most well-known chemi-/bioluminescent systems, and in which reaction the chemi-/bioluminophore (Coelenteramide) is generated and chemiexcited to singlet excited states (leading to light emission). Recent studies have shown that the bromination of compounds associated with the marine Coelenterazine system can provide them with new properties, such as anticancer activity and enhanced emission. Given this, our objective is to characterize the photophysical properties of a previously reported brominated Coelenteramide analog, by employing a combined experimental and theoretical approach. To better analyze the potential halogen effect, we have also synthesized and characterized, for the first time, two new fluorinated and chlorinated Coelenteramide analogs. These compounds show similar emission spectra in aqueous solution, but with different fluorescence quantum yields, in a trend that can be correlated with the heavy-atom effect (F > Cl > Br). A blue shift in emission in other solvents is also verified with the F-Cl-Br trend. More relevantly, the fluorescence quantum yield of the brominated analog is particularly sensitive to changes in solvent, which indicates that this compound has potential use as a microenvironment fluorescence probe. Theoretical calculations indicate that the observed excited state transitions result from local excitations involving the pyrazine ring. The obtained information should be useful for the further exploration of halogenated Coelenteramides and their luminescent properties

Investigation of the Superoxide Anion-Triggered Chemiluminescence of Coelenterazine Analogs

Reactive oxygen species (ROS), including superoxide anion, are involved in regulating various signaling pathways and are also responsible for oxidative stress. Sensing superoxide anion is of particular importance due to its biological significance. One potential approach is to use Coelenterazine as a chemiluminescent probe for the dynamic sensing of this ROS. In this study, we investigated the superoxide anion-triggered chemiluminescence of native Coelenterazine and two halogenated analogs and found that they showed a similar to 100-fold enhancement of light emission in aqueous solution, which was significantly reduced in methanol and nonexistent in aprotic solvents. In fact, Coelenterazine showed more intense light emission in aprotic solvents and, interestingly, although the light emission of the analogs seemed relatively unaffected by the solvents, their chemiluminescence was significantly quenched in water compared to methanol and, especially, to aprotic media. This suggests that the quenching effect observed for Coelenterazine is responsible for the differences in aqueous media, rather than an intrinsic enhanced emission by the analogs. In summary, we present Coelenterazine analogs that could serve as a basis for enhanced sensing of superoxide anion, providing information that could further our understanding of this chemiluminescent system

Comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine

Cancer is still one of the most challenging diseases to treat, making the pursuit for novel molecules with potential anticancer activity an important research topic. Herein, we have performed a comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine. The former is a well-known bioluminescent substrate, while the latter is a metabolic product of the resulting bioluminescent reaction. While both types of analogs showed anticancer activity toward lung and gastric cancer cell lines, we have obtained data that highlight relevant differences between the activity of these two types of compounds. More specifically, we observed relevant differences in structure-activity relationships between these types of compounds. Also, coelenteramine analogs showed time-dependent activity, while coelenterazine-based compounds usually present time-independent activity. Coelenterazine analogs also appear to be relatively safer toward noncancer cells than coelenteramine analogs. There was also seen a correlation between the activity of the coelenterazine-based compounds and their light-emission properties. Thus, these results further indicate the potential of the marine coelenterazine chemi-/bioluminescent system as a source of new molecules with anticancer activity, while providing more insight into their modes of action

Investigation of the Anticancer and Drug Combination Potential of Brominated Coelenteramines toward Breast and Prostate Cancer

Cancer is a very challenging disease to treat, both in terms of therapeutic efficiency and harmful side effects, which continues to motivate the pursuit for novel molecules with potential anticancer activity. Herein, we have designed, synthesized, and evaluated the cytotoxicity of different brominated coelenteramines, which are metabolic products and synthesis precursors of the chemi-/bioluminescent system of marine coelenterazine. The evaluation of the anticancer potential of these molecules was carried out for both prostate and breast cancer, while also exploring their potential for use in combination therapy. Our results provided further insight into the structure-activity relationship of this type of molecule, such as their high structural specificity, as well highlighting the 4-bromophenyl moiety as essential for the anticancer activity. The obtained data also indicated that, despite their similarity, the anticancer activity displayed by both brominated coelenteramines and coelenterazines should arise from independent mechanisms of action. Finally, one of the studied coelenteramines was able to improve the profile of a known chemotherapeutic agent, even at concentrations in which its anticancer activity was not relevant. Thus, our work showed the potential of different components of marine chemi-/bioluminescent systems as novel anticancer molecules, while providing useful information for future optimizations

Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect

Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. Herein, we evaluated the heavy-atom effect as a strategy to provide anticancer activity to derivatives of coelenterazine, a chemiluminescent single-molecule widespread in marine organisms. Our results indicate that the use of the heavy-atom effect allows these molecules to generate readily available triplet states in a chemiluminescent reaction triggered by a cancer marker. Cytotoxicity assays in different cancer cell lines showed a heavy-atom-dependent anticancer activity, which increased in the substituent order of hydroxyl < chlorine < bromine. Furthermore, it was found that the magnitude of this anticancer activity is also dependent on the tumor type, being more relevant toward breast and prostate cancer. The compounds also showed moderate activity toward neuroblastoma, while showing limited activity toward colon cancer. In conclusion, the present results indicate that the application of the heavy-atom effect to marine coelenterazine could be a promising approach for the future development of new and optimized self-activating and tumor-selective sensitizers for light-free PDT

Synchrotron-based FTIR evaluation of biochemical changes in cancer and noncancer cells induced by brominated marine coelenteramine

The mode of action toward gastric cancer cells of brominated Coelenteramine, an analogue of a metabolic product of a marine bioluminescent reaction, was investigated by synchrotron radiation-based Fourier Transform Infrared spectrocopy (FTIR). This method revealed that the anticancer activity of brominated Coelenteramine is closely connected with cellular lipids, by affecting their organization and composition. More specifically, there is an increasing extent of oxidative stress, which results in changes in membrane polarity, lipid chain packing and lipid composition. However, this effect was not observed in a noncancer cell line, helping to explain its selectivity profile. Thus, synchrotron radiation-based FTIR helped to identify the potential of this Coelenteramine analogue in targeting membrane lipids, while proving to be a powerful technique to probe the mechanism of anticancer drugs

Toxicological Study Employing Repeated Doses of Garcinielliptone FC, a Polyisoprenylated-Benzophenone Isolated from Seed of Platonia Insignis Mart

The major constituent from the hexane extract of the seeds of P. insignis is GFC (garcinielliptone FC). Doses of 25, 50and 75 mg/kg of GFC were aseptically suspended in 0.05% Tween 80 dissolved in 0.9% saline (vehicle) and orally administered for30, 90 and 120 consecutive days to adult Swiss mice. In this work, the repeated oral administration, in animals of both sexes,demonstrates that this compound is not able to induce mortality and/or behavioral changes in adult mice. In addition, body weightgain, feed intake and disposal of excreta were not altered by the administration of this compound with repeated doses. Furthermore,no differences in weight and macroscopic structure of the brain, liver, kidney, lung, heart and spleen between groups of male andfemale adult mice were observed after treatment. During the periods of treatment, GFC produced no significant changes onhaematological and biochemical parameters in male and female mice treated with all doses used. The aim of this study was toinvestigate the toxicological potential of GFC through behavioral, hematological, biochemical and morphological parameters inanimals in order to ensure the safe use of Platonia insignis in folk medicine.Fil: Silva, Ana P.. Federal University of Piauí; BrasilFil: Filho, José Carlos C. L. S.. North Union of Parana; BrasilFil: da Costa Júnior, Joaquim S.. Federal Institute of Piauí; BrasilFil: Peláez, Walter José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Faillace, Martín Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Falcão Ferraz, Alexandre de B.. Lutheran University of Brazil; BrasilFil: David, Jorge M.. Institute Of Chemistry, Federal University Of Bahia; Brasil. Universidade Federal da Bahia; BrasilFil: Freitas, Rivelilson M.. Federal University of Bahia; Brasi