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  • Open access
  • 105 Reads
A New Fluorogenic Substrate for Granzyme B Based on Fluorescence Resonance Energy Transfer

The serine protease Granzyme B (GzmB) is a potent inducer of apoptosis in target cells when released by cytotoxic T lymphocytes (CTL) or natural killer (NK) cells, representing one of the two dominant mechanisms by which T cells mediate cancer cell death. Considering the GzmB´s preference for cleaving after aspartic acid, several substrates containing IEPD and IETD sequences coupled to chromogenic or fluorescent leaving groups have been successfully used for GzmB detection. These two sequences, however, lack specificity as they can also be cleaved by some caspases. Also, the use of probes based on fluorescence resonance energy transfer (FRET) principle can have significant advantages over these singly-labelled probes.

Considering our interest in using FRET-based techniques to monitor GzmB activity in a controlled release system of immunostimulating drugs applied in the treatment of colorectal cancer, we reported herein the synthesis and characterization of a new fluorogenic GzmB substrate. For this, our substrate design was based on the FRET principle using 5-(2´-aminoethyl)aminonaphthalene sulfonic acid (Edans) and 4-[[4´-(N,N-dimethylamino)phenyl]diazenyl]benzoic acid (Dabcyl) as the energy transfer pair, linked to a specific sequence for GzmB (AAD), with an additional amino acid as anchoring point (K). The tetrapeptide was obtained by microwave assisted solid phase peptide synthesis and coupled to Dabcyl and Edans at its N- and C-termini, respectively. The obtained probe was purified by semi-preparative HPLC and characterized by NMR, UV/Vis absorption and fluorescence spectroscopy.

  • Open access
  • 89 Reads
A study about the use of Co or Mn-based nanocatalysts for styrene epoxidation reaction

Epoxides are very useful synthetic intermediates as they can be easily converted into a wide variety of products through different chemical transformations on the reactive oxirane ring. Despite many methodologies for the synthesis of epoxides have been reported, efficient and selective epoxidation of olefins remains a challenge. Currently, research is focused on easy-to-use and environmentally friendly oxidants such as O2, TBHP, air or H2O2, together with a transition metal catalyst that helps to improve the reactivity and selectivity of the oxygen transfer process. In this work, Mn- or Co-based nanocatalysts have been studied for styrene epoxidation. These earth-abundant and low-cost metals are known to be part of biologically relevant complexes, such as porphyrins with a pivotal role in oxidation reactions. Co or Mn nanoparticles (NPs) were synthesized by fast reduction of the corresponding metal chlorides, with an excess of Li sand and a catalytic amount of an arene as electron carrier. The metal NPs thus obtained were immobilized on different materials: celite, zeolite, C act., CeO2, ZnO, MgO and Nb2O5. Reaction conditions were optimized by testing different solvents (CH2Cl2, DMF and ACN), reaction temperatures, oxidizing agents (O2, H2O2 and TBHP) and optimal catalyst loading. The progress of the reaction is controlled by CG-MS. The use of CoNPs/MgO as the catalyst and TBHP as co-oxidant, in refluxing ACN, allowed total conversion with high selectivity to the corresponding styrene oxide, after 24 hours of reaction time.

  • Open access
  • 65 Reads

HIV is one of the most deadly viruses known to humans. It causes a disease, known as Acquired Immuno Deficiency Syndrome (or, AIDS). HIV-AIDS, is one of those deadly diseases, which is a fatal disease. There are only a handful drugs which are totally effective against the virus. This is due to the enzyme, reverse transcriptase, present within the virus. Due to various mutations in the enzyme, the virus becomes unresponsive towards the drugs. In the present study, the docking studies of the standard non-nucleoside reverse transcriptase inhibitors were done, in the non nucleoside inhibitory binding pocket of reverse transcriptase enzymes of wild type and the resistant strains of HIV-1RT virus with PDB ID’s- 1RT2, 1KLM, 3BGR and 1JLB respectively by using Autodock version 4.5.6. Comparison of different compounds docked into the active site of various HIV-1RT strains was carried out. The obtained results indicate that most of the compounds docked into the active site of the different receptors, such as- 1RT2,1KLM, 3BGR and 1JLB, with good docking scores, comparable to that of the internal standard (TNK 651) of the wild type strain of HIV-1 virus. A comparison was made based on the binding modes of the compounds in the active site of all the four receptors.

  • Open access
  • 80 Reads
Direct arylation-based synthesis of carbazoles using an efficient palladium nanocatalyst under microwave irradiation

9H-carbazole is a relevant structural scaffold present in a large number of bioactive natural products and drugs with a wide spectrum of therapeutic action. Additionally, 9H-carbazoles are used as building blocks for organic materials, such as polymeric light-emitting diodes (PLED) and organic light-emitting devices (OLED). Therefore, the development of efficient protocols for the generation of structurally diverse carbazoles represents an important synthetic objective in the field of organic synthesis. Many methods have been developed for the preparation of carbazoles. The most widely used approaches to the synthesis of the carbazole nucleus require an intramolecular cyclization forming C-N or C-C bonds from advanced precursors such as substituted biaryls or N,N-diarylamines.

Herein, an eco-friendly palladium-catalyzed tandem reaction for the one-pot synthesis of carbazoles under microwave irradiation is reported. This approach involves an amination and a direct arylation from available and inexpensive anilines and 1,2-dihaloarenes. For the development of this purpose, a novel recoverable palladium nanocatalyst supported on a green biochar under ligand-free conditions is used. Compared to other existing palladium-based protocols, the present synthetic methodology shows a drastic reduction in reaction times and excellent compatibility with different functional groups allowing to obtain a small library of carbazoles with high yields and regioselectivity. The novel heterogeneous palladium nanocatalyst can be recycled and reused up to four 5 times without significant loss activity.

  • Open access
  • 57 Reads
On the acylation of 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles

1,6-Diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles, prepared by reaction of cyanoacethydrazide with arylmethylene malononitriles, react with 1-cyanoacetyl-3,5-dimethylpyrazole and chloroacetyl chloride to give corresponding cyanoacetamides and chloroacetamides. The reaction with phthalic anhydride proceed under harsh conditions to give 4,7-dioxo-4,7-dihydropyrido[1',2':2,3][1,2,4]triazolo[5,1-a]isoindole-1,3-dicarbonitriles.

  • Open access
  • 77 Reads
Microwave-assisted Asinger synthesis of thiazolines

An array of 2,4-disubstituted thiazolines was obtained through Asinger reaction approach from the straightforward treatment of diverse aldehydes/ketones with 1-mercaptopropan-2-one in presence of NH3 assisted by microwave irradiation displaying similar and sometimes higher yields as well as shorter reaction times that traditional Asinger rection conditions at room and lower temperatures.

  • Open access
  • 81 Reads
Synthesis of conjugated polymer based in Zn(II) porphyrin bearing terminal alkynyl groups as photosensitizer

Porphyrins immobilized on a surface have been proposed for the photodynamic inactivation of microorganisms, considering economic and ecological subjects. In hospitals, surfaces are one of the main components of possible reservoirs of bacteria, which can cause a notable incidence in nosocomial infections. In this sense, the coating of surfaces with photosensitizers that are immobilized in a film are of great interest to maintain aseptic surfaces in public health.

In this study, 5,10,15,20-tetrakis-[4-(ethynyl)phenyl]porphyrin (TEP) was synthesized from the condensation of 4-(ethynyl)benzaldehyde and pyrrole catalyzed by boron trifluoride diethyl etherate in dichloromethane (DCM). After oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and purification, TEP was obtained in 38% yield. This porphyrin was metaled with zinc(II) acetate in DCM/methanol to produce the complex ZnTEP in 98% yield. Homocoupling reaction of terminal alkynes of ZnTEP to diynes was used to synthesize conjugated polymer organogel cocatalyzed by PdCl2(PPh3)2 and CuI in THF. Solvent was evaporated to obtain xerogel and the SEM images showed microporous structure. In addition, spectroscopic and photodynamic studies indicated that the porphyrin unit retains its properties as photosensitizer. Thus, this polymer is an interesting material with potential applications to form photoactive aseptic surfaces.

  • Open access
  • 62 Reads
Stokesia aster ethanolic extract activity on the normal and malignant murine cell line viability L969 and B16

We studied the cytotoxic and anti-proliferative potential of the ethanolic extract (Slae26) from Stokesia laevis on normal murine fibroblast cell line L929 and malignant murine melanoma cell line B16, respectively.

The cytotoxicity test on the normal murine fibroblast cell line L929 indicated that Slae26 test sample concentrations less than 25 μg/ml induced moderate stimulating effects on the L929 cell line viability, after that there were noticed augmented inhibitory activity (up to 84% cell viability decrease at 100 μg/ml); similarly, the anti-proliferative test indicated that, less than 10 μg/mL extract at 24 hours/h, and less than 5 μg/mL at 48 h, Slae26 test sample induced stimulating effects, after which the same decrease in cell viability was observed. Regarding malignant murine melanoma cell line B16, the cytotoxicity test shown the same stimulating effects on the B16 cell line, followed by a severe decrease in cell viability at higher concentrations; similarly, the anti-proliferative test indicated less than 10 μg/mL extract at 24h, and less than 5 μg/mL at 48h, Slae26 extract induced stimulating effects on B16 cell line viability (up to 20% and up to 18%, at 24 h and 48 h, respectively), followed by a sharp decrease in cell viability at 24 and 48 h.

Results on molecular docking approach on the major components of Slae26 against human tyrosinase receptor to evaluate possible melanogenesis inhibition, are also presented.

  • Open access
  • 103 Reads
In silico evaluation of antimicrobial activity of some thiadiazoles using molecular docking approach

Molecular docking studies have been performed to assess antimicrobial potential of three 1,3,4-Thiadiazole derivatives containing azulene rings. The simulations were conducted on Mycobacterium tuberculosis DNA gyrase reaction core (PDB ID 3M4I), Staphylococcus aureus DNA gyrase (PDB ID 4P8O) and Escherichia coli DNA adenine methylase (PDB ID 4RTO). The relationships between the structures of compounds and their potential antimicrobial activity were investigated. Interactions with proteins fragment amino acids residues form the active binding site were elucidated and the results of docking are reported in terms of docking score, compared with the natural ligand behaviour. Better docking scores are obtained for all the investigated compounds than for the natural ligand, the co-crystalized (4S)-2-methyl-2,4-pentanediol, in the case of the Mycobacterium tuberculosis DNA gyrase. Two of the studied ligands present better binding affinities against Escherichia coli DNA Adenine Methyltransferase (DAM) than the natural ligand (Sinefungin). Regarding S. aureus gyrase, the investigated thiadiazole derivatives exhibit lower docking scores and less interactions than the natural aminobenzimidazole urea inhibitor. Our study can be useful to screen and design new active compounds possessing similar structural moieties.

  • Open access
  • 69 Reads
Preparation of novel complexes bearing diphosphine (dppm) derived from thiosemicarbazone palladacycles

The synthesis of palladium cyclometallated compounds with thiosemicarbazone ligands is described,as well as their reactivity with bidentate phosphine ligands. The synthesis of the ligands is carried out by a condensation reaction between a ketone and a thiosemicarbazide. Subsequently, metallation proceeds, and the resulting product is reacted with the bis(diphenylphosphino)methane (dppm) using the appropriate conditions to obtain the compound with phosphine in a monodentate coordination mode.