Synthesis, physical and magnetic properties of BaFe12O19/P(VDF-TrFE) multifunctional composites

Composite films with filler microparticles of Barium ferrite dispersed within P(VDF-TrFE) as polymeric matrix have been prepared by solvent evaporation. The lowest BaFO content of 1% wt acts as a small defect within the polymeric matrix, reducing the values of the dielectric and mechanical properties of the pure P(VDF-TrFE). For filler contents up to a 20%, the BaFO filler reinforces the matrix and measured properties increase their values. This trend is not followed by the electrical conductivity. We extended the study to fibers composed by BaFe12O19 microparticles in a PVDF matrix. Due to the big size of BaFO particles (1 micron in diameter), proper fabrication of the fiber shaped composites has not been achieved. We found that true BaFO content are always lower than nominal ones. Results are discussed in terms of the influence of size and morphology of the BaFO particles on the initial properties of the polymeric matrix.

One-step in situ synthesis of polyamide microcapsules with inorganic payload and their transformation into responsive thermoplastic composite materials

Well-dispersed loads of finely powdered metals, metal oxides, several carbon allotropes or nanoclays are incorporated into highly porous polyamide 6 microcapsules in controllable amounts via an original one-step in situ fabrication technique. It is based on activated anionic polymerization (AAP) of ε-caprolactam in a hydrocarbon solvent performed in the presence of the respective micro- or nanosized loads. The forming microcapsules with typical diameters of 25-50 µm entrap up to 40 wt% of load. Their melt processing produces hybrid thermoplastic composites. Mechanical, electric conductivity and magnetic response measurements show that transforming of in situ loaded microcapsules into composites by melt processing (MP) is a facile and rapid method to fabricate materials with high mechanical resistance and electro-magnetic characteristics sufficient for many industrial applications. This novel concept requires low polymerization temperatures, no functionalization or compatibilization of the loads and it is easy to scale up at industrial production levels.

Synthesis and anticancer activity of N3-substituted-6,8-diaminopurines

[Excerpt] Cancer is the second most common cause of death in developed countries appearing just after cardiovascular diseases. The treatment of cancer remains a major medical challenge and the development of new anticancer drugs is an emerging topic for the scientific community. During the past three decades several chemical classes of anticancer drugs have been identified. In particular, 2,6-diamino purines proved to be important candidates as new anti-cancer agents.

A new and efficient synthesis of N3-cycloalkylamino-6,8-diaminopurines

[Excerpt] The purine core is a privileged scaffold in medicinal chemistry and the biological relevance of purine derivatives makes them attractive targets in the preparation of combinatorial libraries.1,2 In particular, there is a great interest in the synthesis of 8-substituted purines due to their important potential as antiviral and anticancer agents.3 Reports on 8-aminopurines are limited and general methods to obtain these purine derivatives are still needed.4 Cyclic amines and hydrazines are key structural motifs in various bioactive agents.5 Here we report a novel, efficient and inexpensive method for the synthesis of 6,8-diaminopurines 4 incorporating cycloalkylamino substituents at N3position of the purine ring. (...)

A new and efficient synthesis of benzoimidazopurine derivatives

[Excerpt] Purine nucleobases are essential biomolecules in living organisms. Playing several key roles in the cell, they have been a significant inspiration for drug design.1 Benzimidazole nucleus is an important pharmacophore in the development of molecules with pharmaceutical or biological interest. Benzimidazoles have been reported to display significant pharmacological activities such as antiulcer, antifungal, antiparkinson, anticancer and antibiotic.2 Fused structures incorporating these two scaffolds might be important for medicinal chemistry and, to the best of our knowledge, there are no reports of these systems in the literature. In particular, benzo[4,5]imidazo[2,1]purines seem to be novel and must be important target molecules in the heterocyclic synthesis. (...)

The synthesis of new 6-hydrazinopurines as potential anticancer agents

[Excerpt] Purines, such as adenine, are one of the most important naturally occurring nitrogen heterocycles and they are frequently used as bioactive agents.[1,2] The increasing number of synthetic purines reveals the great potential of these compounds as enzyme inhibitors. Protein Kinases have an important regulatory role in cell proliferation, differentiation and signalling processes. Abnormal signal transduction is responsible for devastating diseases such as cancer. All of the protein kinases identified have in common the cofactor ATP indicating that the adenine nucleus is a very important scaffold for discovery of new anti-cancer agents.[3,4] Previous work identified a modest anticancer activity in a family of 6-arylaminopurines. In the view of these results, it seemed reasonable to assume that some interesting anticancer agents might result by replacement of the phenyl group by a secondary amino group linked to the N-6 atom of the adenine moiety. (...)

The synthesis of novel 5-aminoimidazoles derivatives with anticancer activity

[Excerpt] The imidazole nucleus is present in a significant number of biomolecules and the inclusion of this moiety in organic scaffolds is considered an important synthetic strategy in drug discovery.[1] 5-Aminoimidazoles are interesting building blocks in medicinal chemistry since they are key components in many bioactive molecules and their derivatives showed a wide pharmacological potential as anticancer drugs.[1] The hydrazones constitute an important class of biological active drug molecules due to their wide range of pharmacological properties that include antitumoral activities.[2] Amidrazone derivatives could be considered very promising in the perspective of new drug discovery, because they are very effective as building blocks to obtain various heterocycles.[2,3] The α-hydrazononitriles are a special case of compounds belonging to the family of hydrazones that is less common in the literature, but has a great interest due to their pharmacological applications.[4] (...)

Peptaibolin analogues by incorporation of α,α-dialkylglycines: synthesis and study of their membrane permeating ability

Analogues of Peptaibolin, a peptaibol with antibiotic activity, incorporating α,α-dialkylglycines (Deg, Dpg, and Ac6c) at selected positions were synthesised by MW-SPPS and fully characterized. A control analogue incorporating L-alanine was also prepared. The native peptide and the analogues were studied by fluorescence spectroscopy for their membrane permeating activity. Small unilamellar vesicles (SUVs) of egg phosphatidylcholine/ cholesterol (70:30) containing an encapsulated fluorescence probe (6-carboxyfluorescein) were used as membrane models. The assays of carboxyfluorescein release from SUVs upon peptide addition showed that Peptaibolin-Dpg and Peptaibolin-Ac6c are the most active peptides. These results indicate that the structure of the α,α-dialkylglycines is crucial for the membrane permeating ability of these Peptaibolin analogues.

Synthesis of polyhydroxylated compounds from Derythrose: enzymatic inhibition studies

Dissertação de mestrado em Química Medicinal

Synthesis of five-membered heterocycles by indirect electrochemical approach in "Green" media

Radical cyclization continues to be a central methodology for the preparation of natural products containing heterocyclic rings. Hence, some electrochemical results obtained by cyclic voltammetry and controlled-potential electrolysis in the study of electroreductive intramolecular cyclization of ethyl (2S, 3R)-2-bromo-3-propargyloxy-3-(2’,3’,4’,6’-tetra-O-acetyl-beta-D-glucopyranosyloxy) propanoate (1a), 2-bromo-3-allyloxy-3-(2’,3’,4’,6’-tetra-O-acetyl-beta-D-glucopyranosyloxy)propanoate (1b), 2-bromo-[1-(prop-2-yn-1-yloxy)propyl]benzene (1c) and [1-bromo-2-methoxy-2-(prop-2’-yn-1-yloxy)ethyl]benzene (1d) promoted by (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane)nickel(I), [Ni(tmc)]+, electrogenerated at glassy carbon cathodes in ethanol and ethanol:water mixtures containing tetraalkylammonium salts, are presented. During controlled-potential electrolyses of solutions containing [Ni(tmc)]2+ and bromoalkoxylated compounds (1) catalytic reduction of the latter proceeds via one-electron cleavage of the carbon–bromine bond to form a radical intermediate that undergoes cyclization to afford the substituted tetrahydrofurans.

Imidazo-benzocrown ether functionalised amino acids: synthesis and fluorimetric chemosensing studies with metal cations

Comunicação em painel - P59

Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-Aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC50 10-28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 microM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.

Synthesis of iminosugars through diastereo/enantioselective diels-alder cycloaddition

Tese de Doutoramento em Ciências (Especialidade em Química)

Systems biology approaches for the design of novel Saccharomyces cerevisiae winemaking strains for enhanced flavour compounds synthesis

Tese de Doutoramento em Biologia Ambiental e Molecular

Ultrasound enhances lipase-catalyzed synthesis of poly (ethylene glutarate)

The present work explores the best conditions for the enzymatic synthesis of poly (ethylene glutarate) for the first time. The start-up materials are the liquids; diethyl glutarate and ethylene glycol diacetate, without the need of addition of extra solvent. The reactions are catalyzed by lipase B from Candida antarctica immobilized on glycidyl methacrylate-ter-divinylbenzene-ter-ethylene glycol dimethacrylate at 40 °C during 18 h in water bath with mechanical stirring or 1 h in ultrasonic bath followed by 6 h in vacuum in both the cases for evaporation of ethyl acetate. The application of ultrasound significantly intensified the polyesterification reaction with reduction of the processing time from 24 to 7 h. The same degree of polymerization was obtained for the same enzyme loading in less time of reaction when using the ultrasound treatment. The degree of polymerization for long-term polyesterification was improved approximately 8-fold due to the presence of sonication during the reaction. The highest degree of polymerization achieved was 31, with a monomer conversion of 96.77%. The ultrasound treatment demonstrated to be an effective green approach to intensify the polyesterification reaction with enhanced initial kinetics and high degree of polymerization.