Fluorescent quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and m... more Fluorescent quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and mass spectrometry. We measured their cytotoxic activity against cancer and normal cell lines, performed mechanistic studies by lipid peroxidation and determination of reduced (GSH) and oxidized (GSSG) glutathione, and imaged their subcellular localisation by confocal microscopy. Cell imaging experiments indicated that nor-β-lapachone-based BODIPY derivatives might preferentially localise in the lysosomes of cancer cells. These results assert the potential of hybrid quinone-BODIPY derivatives as promising prototypes in the search of new potent lapachone antitumor drugs.
Delonix is a galactomannan polysaccharide extracted from the endosperm of Delonix regia plant. Th... more Delonix is a galactomannan polysaccharide extracted from the endosperm of Delonix regia plant. This study aims at the development of Delonix nanoparticle and assesses its potential for ocular delivery by evaluating its in-vitro stability, toxicity and cellular uptake. Fluorescent nanoparticles (BODIPY-loaded nanoparticles) were prepared by a Quality-by-Design modified nanoprecipitation technique. Optimized nanoparticles had mean sizes <240nm, PdI<0.2 and zeta potential of <-30mV. Mixture of surfactants with different hydrophilic-lipophilic balance controlled nanoparticle swelling. Nanoparticles, which were stable in the presence of simulated lachrymal fluid and lysozyme also sustained the release of BODIPY. In-vitro studies suggest no toxicity of the nanoparticles in concentration range of 100-1483.3μg/mL on retinal and corneal epithelial cells. Flow cytometry and confocal microscopy techniques showed that retinal cells but not corneal cells, uptake 18% of the nanoparticles...
Bioorganic & medicinal chemistry letters, Jan 14, 2016
Chagas disease continues to be a difficult disease to eradicate, largely because of the widesprea... more Chagas disease continues to be a difficult disease to eradicate, largely because of the widespread populations it affects as well as the highly toxic effects of current therapies. Thus, the exploration of innovative scaffolds, ideally with distinct mechanisms of action, is urgently needed. The natural product aphidicolin and its effects on cell cycle division have been widely studied; it is a potent inhibitor of parasitic cells. In the present study, we report for the first time the semisynthesis of a series of aphidicolin derivatives, their unique structural features, and demonstration of their activity against Trypanosoma cruzi cells. Two demonstrated high potency and selectivity against parasitic amastigote cells, and thus show promise as new leads for Chagas disease treatment.
LSD-1 is an enzyme that removes methyl groups from lysine residues of histone proteins. LSD-1 inh... more LSD-1 is an enzyme that removes methyl groups from lysine residues of histone proteins. LSD-1 inhibition decreases cellular proliferation and therefore represents a therapeutic target for cancer treatment. MAO and LSD-1 are both flavin adenine dinucleotide-dependent MAOs, and the MAO inhibitor, tranylcypromine, is currently undergoing clinical trials for cancer treatment because it acts as an irreversible LSD-1 inhibitor. The present study investigated new reversible LSD-1 inhibitors, in order to develop novel selective anticancer agents. We constructed 2 and 3D quantitative structure-activity relationship models by using a series of 54 aminothiazole and thiazolesulfonamide derivatives. The models were validated internally and externally (q(2) , 0.691 and 0.701; r(2) , 0.894 and 0.937; r(2) test , 0.785 and 0.644, for 2 and 3D models, respectively). Fragment contribution maps, as well as steric and electrostatic contour maps were generated in order to obtain chemical information rel...
Journal of controlled release : official journal of the Controlled Release Society, Jan 29, 2014
Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain ... more Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain therapeutic concentrations. Fourth generation polyamidoamine (PAMAM) dendrimers are semi-rigid nanoparticles with surface groups that are easily modified. These dendrimers are known to modulate tight junctions, increase paracellular transport of small molecules and be translocated across epithelial barriers, exhibiting high uptake by different cell lines. The first aim of this study was to investigate the effect of iontophoresis on PAMAM penetration and distribution into the cornea. The second aim was to evaluate, ex vivo and in vivo, the effect of these dendrimers in dexamethasone (Dex) transcorneal iontophoresis. Anionic (PAMAM G3.5) and cationic (PAMAM G4) dendrimers were labeled with fluorescein isothiocyanate (FITC), and their distribution in the cornea was investigated using confocal microscopy after ex vivo anodal and cathodal iontophoresis for various application times. The parti...
Fluorescent quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and m... more Fluorescent quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and mass spectrometry. We measured their cytotoxic activity against cancer and normal cell lines, performed mechanistic studies by lipid peroxidation and determination of reduced (GSH) and oxidized (GSSG) glutathione, and imaged their subcellular localisation by confocal microscopy. Cell imaging experiments indicated that nor-β-lapachone-based BODIPY derivatives might preferentially localise in the lysosomes of cancer cells. These results assert the potential of hybrid quinone-BODIPY derivatives as promising prototypes in the search of new potent lapachone antitumor drugs.
Delonix is a galactomannan polysaccharide extracted from the endosperm of Delonix regia plant. Th... more Delonix is a galactomannan polysaccharide extracted from the endosperm of Delonix regia plant. This study aims at the development of Delonix nanoparticle and assesses its potential for ocular delivery by evaluating its in-vitro stability, toxicity and cellular uptake. Fluorescent nanoparticles (BODIPY-loaded nanoparticles) were prepared by a Quality-by-Design modified nanoprecipitation technique. Optimized nanoparticles had mean sizes <240nm, PdI<0.2 and zeta potential of <-30mV. Mixture of surfactants with different hydrophilic-lipophilic balance controlled nanoparticle swelling. Nanoparticles, which were stable in the presence of simulated lachrymal fluid and lysozyme also sustained the release of BODIPY. In-vitro studies suggest no toxicity of the nanoparticles in concentration range of 100-1483.3μg/mL on retinal and corneal epithelial cells. Flow cytometry and confocal microscopy techniques showed that retinal cells but not corneal cells, uptake 18% of the nanoparticles...
Bioorganic & medicinal chemistry letters, Jan 14, 2016
Chagas disease continues to be a difficult disease to eradicate, largely because of the widesprea... more Chagas disease continues to be a difficult disease to eradicate, largely because of the widespread populations it affects as well as the highly toxic effects of current therapies. Thus, the exploration of innovative scaffolds, ideally with distinct mechanisms of action, is urgently needed. The natural product aphidicolin and its effects on cell cycle division have been widely studied; it is a potent inhibitor of parasitic cells. In the present study, we report for the first time the semisynthesis of a series of aphidicolin derivatives, their unique structural features, and demonstration of their activity against Trypanosoma cruzi cells. Two demonstrated high potency and selectivity against parasitic amastigote cells, and thus show promise as new leads for Chagas disease treatment.
LSD-1 is an enzyme that removes methyl groups from lysine residues of histone proteins. LSD-1 inh... more LSD-1 is an enzyme that removes methyl groups from lysine residues of histone proteins. LSD-1 inhibition decreases cellular proliferation and therefore represents a therapeutic target for cancer treatment. MAO and LSD-1 are both flavin adenine dinucleotide-dependent MAOs, and the MAO inhibitor, tranylcypromine, is currently undergoing clinical trials for cancer treatment because it acts as an irreversible LSD-1 inhibitor. The present study investigated new reversible LSD-1 inhibitors, in order to develop novel selective anticancer agents. We constructed 2 and 3D quantitative structure-activity relationship models by using a series of 54 aminothiazole and thiazolesulfonamide derivatives. The models were validated internally and externally (q(2) , 0.691 and 0.701; r(2) , 0.894 and 0.937; r(2) test , 0.785 and 0.644, for 2 and 3D models, respectively). Fragment contribution maps, as well as steric and electrostatic contour maps were generated in order to obtain chemical information rel...
Journal of controlled release : official journal of the Controlled Release Society, Jan 29, 2014
Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain ... more Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain therapeutic concentrations. Fourth generation polyamidoamine (PAMAM) dendrimers are semi-rigid nanoparticles with surface groups that are easily modified. These dendrimers are known to modulate tight junctions, increase paracellular transport of small molecules and be translocated across epithelial barriers, exhibiting high uptake by different cell lines. The first aim of this study was to investigate the effect of iontophoresis on PAMAM penetration and distribution into the cornea. The second aim was to evaluate, ex vivo and in vivo, the effect of these dendrimers in dexamethasone (Dex) transcorneal iontophoresis. Anionic (PAMAM G3.5) and cationic (PAMAM G4) dendrimers were labeled with fluorescein isothiocyanate (FITC), and their distribution in the cornea was investigated using confocal microscopy after ex vivo anodal and cathodal iontophoresis for various application times. The parti...
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Papers by Flavio S Emery