Phenolic Imidazole Derivatives with Dual Antioxidant/Antifungal Activity: Synthesis and Structure-Activity Relationship.

Background: Previous publications show that the addition of a phenolic antioxidant to an antifungal agent, considerably enhances the antifungal activity.

Objective: Synthesis of novel compounds combining phenolic units with linear or cyclic nitrogencontaining organic molecules with antioxidant/antifungal activity using methodologies previously developed in the group.

Methods: Several N- [1,2-dicyano-2- (arylidenamino) vinyl]-O-alkylformamidoximes 3 were synthesized and cyclized to 4,5-dicyano-N- (N´-alcoxyformimidoyl)-2-arylimidazoles 4 upon reflux in DMF, in the presence of manganese dioxide or to 6-cyano-8-arylpurines 5 when the reagent was refluxed in acetonitrile with an excess of triethylamine.

Vacuole-mitochondrial cross-talk during apoptosis in yeast: a model for understanding lysosome-mitochondria-mediated apoptosis in mammals.

The yeast apoptosis field emerged with the finding that key components of the apoptotic machinery are conserved in these simple eukaryotes. Thus it became possible to exploit these genetically tractable organisms to improve our understanding of the intricate mechanisms of cell death in higher eukaryotes and of severe human diseases associated with apoptosis dysfunctions. Early on, it was recognized that a mitochondria-mediated apoptotic pathway showing similarities to the mammalian intrinsic pathway was conserved in yeast.

Nitrogen compounds prevent h9c2 myoblast oxidative stress-induced mitochondrial dysfunction and cell death.

Oxidative stress has been connected to various forms of cardiovascular diseases. Previously, we have been investigating the potential of new nitrogen-containing synthetic compounds using a neuronal cell model and different oxidative stress conditions in order to elucidate their potential to ameliorate neurodegenerative diseases. Here, we intended to extend these initial studies and investigate the protective role of four of those new synthetic compounds (FMA4, FMA7, FMA762 and FMA796) against oxidative damage induced to H9c2 cardiomyoblasts by tert-butylhydroperoxide (t-BHP).

Novel nitrogen compounds enhance protection and repair of oxidative DNA damage in a neuronal cell model: comparison with quercetin.

Oxidative DNA damage has been described as an important type of damage that occurs in neuronal cells, with severe implications in many neurodegenerative diseases and in aging. We have previously reported the protection of four new synthetic nitrogen compounds (FMA4, FMA7, FMA762 and FMA796) against oxidative stress conditions. In this work, we studied their effects on oxidative DNA damage induced in rat pheochromocytoma (PC12) cells, using the Comet assay, and compared them with a natural antioxidant, quercetin.

Oxidative DNA damage protection and repair by polyphenolic compounds in PC12 cells.

Biological systems are frequently exposed to excessive reactive oxygen species, causing a disturbance in the cells natural antioxidant defence systems and resulting in damage to all biomolecules, including nucleic acids. In fact, oxidative DNA damage is described as the type of damage most likely to occur in neuronal cells. In this study, three polyphenolic compounds, luteolin, quercetin and rosmarinic acid, were investigated for their protective effects against oxidative DNA damage induced in PC12 cells, a neuronal cell model.

Antioxidant activity of synthetic diarylamines: a mitochondrial and cellular approach.

We investigated the antioxidant properties of two synthetic diarylamines, MJQ1 and MJQ2. For one of them (MJQ1) the synthesis procedure is herein described. The compounds showed maximal protection of ADP/Fe(2+) induced mitochondrial lipid peroxidation for 50nM (MJQ1) and 60muM (MJQ2) concentrations.

Protective role of new nitrogen compounds on ROS/RNS-mediated damage to PC12 cells.

Reactive oxygen (ROS) and nitrogen (RNS) species are known to be involved in many degenerative diseases. This study reports four new nitrogen compounds from organic synthesis, identified as FMA4, FMA7, FMA762 and FMA796, which differ mainly by the number of hydroxyl groups within their phenolic unit. Their potential role as antioxidants was evaluated in PC12 cells by assessing their protection against oxidative and nitrosative insults.

Starch-based microparticles as vehicles for the delivery of active platelet-derived growth factor.

In a previous work, we described the use of starch-based microparticles as vehicles for the controlled release of corticosteroids. The goal of the present work is to evaluate the potential of these microparticles to incorporate and release platelet-derived growth factor (PDGF). The loading efficiency and release profile were evaluated, and PDGF was incorporated into and released from the matrix of starch-based microparticles.

The effect of starch and starch-bioactive glass composite microparticles on the adhesion and expression of the osteoblastic phenotype of a bone cell line.

There is a clear need for the development of microparticles that can be used simultaneously as carriers of stem/progenitor cells and as release systems for bioactive agents, such as growth factors or differentiation agents. In addition, when thinking on bone-tissue-engineering applications, it would be very useful if these microparticles are biodegradable and could be made to be bioactive. Microparticles with all those characteristics could be cultured together with adherent cells in appropriate bioreactors to form in vitro constructs that can then be used in tissue-engineering therapies.

Oxidative stress protection by newly synthesized nitrogen compounds with pharmacological potential.

In this study we used new nitrogen compounds obtained by organic synthesis whose structure predicted an antioxidant potential and then an eventual development as molecules of pharmacological interest in diseases involving oxidative stress. The compounds, identified as FMA4, FMA5, FMA7 and FMA8 differ in the presence of hydroxyl groups located in the C-3 and/or C-4 position of a phenolic unit, which is possibly responsible for their free radicals' buffering capacity. Data from the DPPH discoloration method confirm the high antiradical efficiency of the compounds.

Bone tissue engineering: state of the art and future trends.

Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution.