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

Interferência de plantas daninhas na cultura do sorgo sacarino.

Este trabalho teve como objetivo o estudo fitossociológico da comunidade infestante ao longo do ciclo de desenvolvimento do sorgo sacarino e a determinação do período crítico de prevenção à interferência das plantas daninhas na cultura. O delineamento experimental foi de blocos ao acaso com três repetições. Os tratamentos foram constituídos por períodos crescentes de controle ou convivência das plantas daninhas em diferentes estádios fenológicos da cultura: 0-3 (V3), 0-5 (V5), 0-7 (V7), 0-9 (V9), 0-11(V11) folhas completamente expandidas e 0-R5 (colheita). A comunidade infestante foi avaliada por meio do número de indivíduos e da massa seca acumulada correspondente, para cada população de planta daninha nos diferentes períodos de convivência. O sorgo sacarino foi colhido aos 101 dias após a emergência, quando se avaliaram altura, diâmetro, teor de sólidos solúveis totais (°Brix) em função dos períodos de convivência da cultura com as plantas daninhas, além do rendimento de colmos nos diferentes tratamentos. Commelina benghalensis e Panicum maximum foram as duas espécies de maior importância relativa na área, no momento da colheita. A ausência de controle da comunidade infestante, durante todo o ciclo do sorgo sacarino, ocasionou aumento no teor de sólidos solúveis totais (°Brix) e redução de, respectivamente, 9% e 25% na altura e diâmetro de colmo da cultura, quando comparado com a testemunha capinada durante todo o ciclo. Considerando a tolerância de 5% na redução da produtividade de colmos, observou-se que o período crítico de prevenção a interferência correspondeu ao intervalo do estádio fenológico V3 a V11

Deficiência de cálcio e fósforo em bubalinos no município de Portel, Estado do Pará.

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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

Experimental and computational study of the energetics of hydantoin and 2-thiohydantoin

This work reports an experimental and a theoretical study of two imidazolidine derivatives, hydantoin (CAS No. 461-72-3) and 2-thiohydantoin (CAS No. 503-87-7). The standard (p degrees = 0.1 MPa) molar energies of combustion of hydantoin and 2-thiohydantoin were measured by static and rotating bomb combustion calorimetry, respectively. The standard molar enthalpies of sublimation, at T = 298.15 K, were derived from the temperature dependence of the vapour pressures of these compounds, measured by the Knudsen-effusion technique, and from high temperature Calvet microcalorimetry. The conjugation of these experimental results enables the calculation of the standard molar enthalpies of formation in the gaseous state, at T = 298.15 K, which are discussed in terms of structural contributions. We have also estimated the gas-phase enthalpy of formation from high-level ab initio molecular orbital calculations at the G3MP2B3 level of theory, being the computed values in good agreement with the experimental ones. Furthermore, this composite approach was also used to obtain information about the gas-phase basicities, proton and electron affinities and adiabatic ionization enthalpies

Chemical and physical fractions of soil organic matter under various management regimes in Roraima, Brazil.

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