Showing papers by "Artur M. S. Silva published in 2012"
TL;DR: In this paper, the absolute configuration of the stereogenic carbons of the previously reported tryptoquivalines F, H, L was revised using the data obtained from an X-ray analysis of tryquivaline l and the NOESY correlations, together with four new pyrazinoquinazolinone derivatives (10, 12, 13, 14) were established based on 1D and 2D NMR spectral analysis.
73 citations
TL;DR: The phenolic composition of the ethanolic extract obtained from the flowers of the medicinal plant Cytisus multiflorus has been elucidated by high performance liquid chromatography, electrospray mass spectrometry and nuclear magnetic resonance analysis as discussed by the authors.
70 citations
TL;DR: A new diketopiperazine dimer was isolated, in addition to eight known metabolites including the anthraquinones erythroglaucin, physcion, catenarin, emodin and the dioxopiperazines alkaloids echinulin, neechinulin A, neoechinulin E, variecolorin J, from the culture of the sponge-associated fungus Eurotium cristatum KUFC 7356.
45 citations
TL;DR: Computer-assisted phase-contrast microscopy-related analysis revealed that 2 represented a novel chemical scaffold from which derivatives for anticancer cytostatic compounds can be derived, and did not induce apoptotic features in U373 or A549 cancer cells.
Abstract: Four known (1, 2, 3, and 6) and three new compounds including a 1,4-diacetyl-2,5-dibenzylpiperazine derivative (4), a quinazolinone-containing indole derivative (5), and a new ester of 2,4-dihydroxy-6-methylbenzoic acid (7) were isolated from the fungus Neosartorya pseudofischeri S. W. Peterson. Compound 2 displayed in vitro growth inhibitory activity that ranged between the activities of etoposide and carboplatin, chosen as reference compounds, in six distinct cancer cell lines. Compound 1 displayed less activity than 2. Computer-assisted phase-contrast microscopy-related analysis revealed that 2 displayed cytostatic, not cytotoxic, effects in human U373 glioblastoma and A549 non-small cell lung cancer apoptosis-resistant cells with marked inhibition of mitotic rates. Cancer cells in the remaining phases of the cell cycle were unchanged. Flow cytometry analysis further confirmed that 2 does not induce apoptotic features in U373 or A549 cancer cells. Thus, 2 represents a novel chemical scaffold from which derivatives for anticancer cytostatic compounds can be derived.
42 citations
TL;DR: Thirty-one phenolic metabolites were identified by high-performance liquid chromatography-diode array detection-electrospray ionization/mass spectrometry (HPLC-DAD-ESI/MS(n) in the leaves of two C. esculenta varieties cultivated in Azores Islands and 34 of them are being reported for the first time in this species.
Abstract: Colocasia esculenta (L) Shott, commonly called taro, is an ancient species selected for its edible tuber Its huge "elephant ear" like leaves are also consumed in sauces and stews or as soups Forty-one phenolic metabolites (11 hydroxycinnamic acid derivatives and 30 glycosylated flavonoids) were identified by high-performance liquid chromatography-diode array detection-electrospray ionization/mass spectrometry (HPLC-DAD-ESI/MS(n)) in the leaves of two C esculenta varieties cultivated in Azores Islands To our knowledge, 34 of the 41 phenolic compounds are being reported for the first time in this species Phenolics quantification was achieved by an HPLC-DAD accurate and sensitive validated method Although the qualitative profile of the two varieties is quite similar, quantitative differences were observed between them "Giant white" and "red" varieties (local denomination) contain, respectively, ca 14 and 21% of phenolic acids, 37 and 28% of flavones mono-C-glycosides, 42 and 43% of flavones di-C-glycosides, 3 and 4% of flavones mono-C-(O-glycosyl)glycosides, and both of them ca 2% of flavones di-C-(O-glycosyl)glycosides and 2% of flavones-O-glycosides Luteolin-6-C-hexoside was the compound present in higher amounts in both varieties The established phenolic profile is an added value for the authenticity and quality control of C esculenta and may be useful in the discrimination of its varieties
34 citations
TL;DR: Generally, the tested chalcones interfered with the cell cycle profile and increased the percentage of apoptotic MCF-7 cells, which may help to identify new chalcone-like structures with optimized cell growth inhibitory activity which may be further tested as potential antitumor agents.
32 citations
TL;DR: In this article, a purified ethanolic extract (PEEL) was prepared and further analyzed by high performance liquid chromatography and electrospray mass spectrometry Overall, verbascoside accounted for approximately half of the phenolic content of the extract, but this also contained other bioactive phenolic compounds, namely isoscutellarein derivatives.
32 citations
TL;DR: Modelling studies suggest that full CB1 selectivity over CB2 can be explained by the presence of a pyrazole ring in the structure, and that the antinociception induced by 13 a in the orofacial test could be mediated through peripheral mechanisms.
Abstract: The unwanted psychoactive effects of cannabinoid receptor agonists have limited their development as medicines. These CB1 mediated side effects are due to the fact that CB1 receptors are largely expressed in the Central Nervous System (CNS). Since it is known that CB1 receptors are also located peripherally, there is a growing interest in targeting cannabinoid receptors located outside the brain. A library of chromenopyrazoles designed in analogy to the classical cannabinoid cannabinol were synthesized, characterized and tested for cannabinoid activity. Radiolabeled binding assays were used to determine their affinities at CB1 and CB2 receptors. Structural features required for CB1/CB2 affinity and selectivity were explored using molecular modeling. Within the chromenopyrazoles series, some of them showed to be selective CB1 ligands. These modeling studies suggest that CB1 full selectivity over CB2 can be accounted for the presence of a pyrazole ring in the structure. The functional activities of selected chromenopyrazoles were evaluated in isolated tissues. Behavioral tests, in vivo, were then carried on the most effective CB1 cannabinoid agonist (13a). Chromenopyrazole 13a did not induce modifications in any of the tested parameters on the mouse cannabinoid tetrad, discarding CNS-mediated effects. This lack of agonistic activity in the CNS suggests that it does not readily cross the blood-brain barrier. Moreover, compound 13a can induce antinociception in a peripheral model of orofacial pain in rat. Taking into account the negative results obtained in the hot plate test, it could be suggested that the antinociception induced by 13a in the orofacial test may be mediated through peripheral mechanisms.
31 citations
TL;DR: Results obtained indicate that aromatic π⋅ⓂⓁ⓽⓷⓱Ⓟπ interactions are significantly enhanced by substitution, in a way that correlates with the ability of the interacting aryl rings to establish dispersive interactions.
Abstract: Herein a core scaffold of 1-phenylnaphthalenes and 1,8-diphenylnaphthalenes with different substituents on the phenyl rings was used to study substituent effects on parallel-displaced aromatic π⋅⋅⋅π interactions. The energetics of the interaction was evaluated in gas phase based on the standard molar enthalpies of formation, at T=298.15 K, for the compounds studied; these values were derived from the combination of the results obtained by combustion calorimetry and Knudsen/Quartz crystal effusion. A homodesmotic gas-phase reaction scheme was used to quantify and compare the intramolecular interaction enthalpies in various substituted 1,8-diphenylnaphthalenes. The application of this methodology allowed a direct evaluation of aromatic interactions, and showed that substituent effects on the interaction enthalpy cannot be rationalized solely on classical electrostatic grounds, because no correlation with the σ(meta) or σ(para) Hammett constants was observed. Moreover, the results obtained indicate that aromatic π⋅⋅⋅π interactions are significantly enhanced by substitution, in a way that correlates with the ability of the interacting aryl rings to establish dispersive interactions. A combined experimental and computational approach for calculation of the true aromatic π⋅⋅⋅π interaction energies in these systems, free of secondary effects, was employed, and corroborates the rationale derived from the experimental results. These findings clearly emphasize the role of dispersion and dilute the importance of electrostatic forces on this type of interactions.
29 citations
TL;DR: Compounds 1 and cis -(3 R , 4 R )-4-hydroxymellein were found to show neither antimicrobial nor the in vitro growth inhibitory activities on three human tumor cell lines.
27 citations
TL;DR: The photophysical properties of pyrazoline and pyrazole porphyrin derivatives show that the influence of the heterocyclic substituents is limited by the tendency of these molecules to aggregate as discussed by the authors.
TL;DR: Six prenyl (=3‐methylbut‐2‐en‐1‐yl) chalcones, 2–7, and one natural non‐prenylated chalcone, 1, have been synthesized and evaluated for their in vitro growth‐inhibitory activity against three human tumor cell lines.
Abstract: Six prenyl (=3-methylbut-2-en-1-yl) chalcones (=1,3-diphenylprop-2-en-1-ones), 2–7, and one natural non-prenylated chalcone, 1, have been synthesized and evaluated for their in vitro growth-inhibitory activity against three human tumor cell lines. A pronounced dose-dependent growth-inhibitory effect was observed for all prenylated derivatives, except for 7. The chalcone possessing one prenyloxy group at C(2′), i.e., 2, was the most active derivative against the three human tumor cell lines (5.9
TL;DR: The reaction of 2-formyl-5,10,15,20-tetraphenylporphyrin with aryl methyl ketones and ammonium acetate, in the presence of La(OTf)(3), affords benzoporphyrins and 2-(2,6-diarylpyridin-4-yl) porphyrins.
TL;DR: The bioactive compounds did not show cytotoxic effects to human lymphocytes using the MTT method adapted for non-adherent cells, nor genotoxicity determined by the short-term in vitro chromosomal aberration assay.
TL;DR: In this paper, the in vitro formation of several new diclofenac derivatives, initially resulting from oxidative decarboxylation, similar to what happens in vivo, is revealed.
Abstract: The oxidation of drugs using metalloporphyrins has been the subject of several studies in recent years. Diclofenac, one of the most frequently used anti-inflammatory drugs, is metabolized in humans by cytochrome P450 (CYP) enzymes to hydroxy-derivatives and to some metabolites resulting from oxidative decarboxylation. In this paper, the in vitro formation of several new diclofenac derivatives, initially resulting from oxidative decarboxylation, similar to what happens in vivo, is revealed. Chloro [5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato]manganese(III), [Mn(TDCPP)Cl], and chloro [5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato]manganese(III), [Mn(TPFPP)Cl], are tested in the presence of hydrogen peroxide at room temperature. The new products obtained are fully characterized, three of them being characterized in the solid state using X-ray diffraction studies.
TL;DR: It has been shown that, among the studied XH, only 2,3-bis(3,4-dihydroxyphenyl)-9H-xanthen-9-one (XH9) reduces ˙TocO, though repair depends strongly on the micro-environment.
Abstract: The flavonoid quercetin is known to reduce the α-tocopheroxyl radical (˙TocO) and reconstitute α-tocopherol (TocOH). Structurally related polyphenolic compounds, hydroxy-2,3-diarylxanthones (XH), exhibit antioxidant activity which exceeds that of quercetin in biological systems. In the present study repair of ˙TocO by a series of these XH has been evaluated using pulse radiolysis. It has been shown that, among the studied XH, only 2,3-bis(3,4-dihydroxyphenyl)-9H-xanthen-9-one (XH9) reduces ˙TocO, though repair depends strongly on the micro-environment. In cationic cetyltrimethylammonium bromide (CTAB) micelles, 30% of ˙TocO radicals are repaired at a rate constant of ∼7.4 × 106 M−1 s−1 by XH9 compared to 1.7 × 107 M−1 s−1 by ascorbate. Water-soluble Trolox (TrOH) radicals (˙TrO) are restored by XH9 in CTAB (rate constant ∼3 × 104 M−1 s−1) but not in neutral TX100 micelles where only 15% of ˙TocO are repaired (rate constant ∼4.5 × 105 M−1 s−1). In basic aqueous solutions ˙TrO is readily reduced by deprotonated XH9 species leading to ionized XH9 radical species (radical pKa ∼10). An equilibrium is observed (K = 130) yielding an estimate of 130 mV for the reduction potential of the [˙X9,H+/XH9] couple at pH 11, lower than the 250 mV for the [˙TrO,H+/TrOH] couple. A comparable value (100 mV) has been determined by cyclic voltammetry measurements.
TL;DR: In this paper, the binding mode of the synthesized cationic beta-vinyl-pyridinium and beta-,quinolinium-meso-tetraphenylporphyrin derivatives with a short GC duplex oligonucleotide was investigated.
Abstract: Several cationic beta-vinyl-pyridinium and beta-vinyl-quinolinium-meso-tetraphenylporphyrin derivatives were synthesized starting from 2-formyl-meso-tetraphenylporphyrin, and the corresponding Zn(II) complex, and different N-alkyl derivatives of 2- and 4-methylpyridine and 2- and 4-methylquinoline. The new compounds were obtained in a one-step process via base catalyzed aldol-type condensation reactions. Electrospray ionization mass spectrometry (ESI-MS) and ultraviolet-visible (UV-vis) spectroscopy were used to investigate the binding mode of the synthesized cationic beta-vinyl-pyridinium and beta-vinyl-quinolinium-meso-tetraphenylporphyrin derivatives with a short GC duplex oligonucleotide. Analysis of the obtained mass spectrometry results indicates the probable occurrence of outside binding. UV-vis spectroscopy data also points to non-intercalation. The potential photosensitizing capacity of these compounds was also ascertained from preliminary photophysical studies.
TL;DR: In this paper, a two-step transformation of acridin-9(10 H)-ones was developed, namely the Diels-Alder -reactions of (E)-1-methyl-2-styrylquinolin-4(1H)-ones with N-methylmaleimidein refluxing toluene, followed by oxidation of the formed adducts.
Abstract: New syntheses of acridin-9(10 H)-oneswere developed. One involves a two-step transformation, namely theDiels-Alder -reactions of ( E)-1-methyl-2-styrylquinolin-4(1 H)-ones with N-methylmaleimidein refluxing toluene, followed by oxidation of the formed adducts.The second consists in an one-pot procedure using 1,2,4-trichlorobenzeneas solvent at 180 ˚C. The effect of microwave irraditionand Lewis acid catalysts in these cycloaddition -reactionswas also investigated.
TL;DR: Novel 5-amino-1H-1,2,3-triazoles were synthesized by a new synthetic route that involves consecutive tandem cycloaddition between nitriles and azides.
Abstract: Novel 5-amino-1H-1,2,3-triazoles were synthesized by a new synthetic route that involves consecutive tandem cycloaddition between nitriles and azides.
TL;DR: In this paper, the use of microwave irradiation led to an improvement in the yields of both the Knoevenagel condensation of β-diketones with aldehydes to afford 3-aroylflavanones and of their oxidation to 3-ARoylflavones.
Abstract: Two syntheses of 3-aroylflavones have been established. In the first synthesis the use of microwave irradiation led to an improvement in the yields of both the Knoevenagel condensation of β-diketones with aldehydes to afford 3-aroylflavanones and of their oxidation to 3-aroylflavones. In the second and more general synthesis, a novel and efficient procedure for 3-aroylflavones involves a one-pot reaction between 2′-hydroxyacetophenones and aroyl chlorides in the presence of lithium bis(trimethylsilyl)amide.
TL;DR: In this article, a mixture of diastereoselectivity arises from the combination of the pyrazoline C-4 stereocenter and two planar chiral subunits due to internal steric hindrance.
Abstract: Novel 3-aryl-5-{4-[5-(2-hydroxyphenyl)-1-phenylpyrazolyl]}-2-pyrazolines 2a-g have been prepared by the treatment of 3-(3-aryl-3-oxopropenyl)chromen-4-ones 1a-g with phenylhydrazine in refluxing acetic acid. NMR studies on deuteriochloroform solutions of pyrazolyl-2-pyrazolines 2a-g at different temperatures showed that at room temperature a mixture of diastereomers are present. This diastereoselectivity arises from the combination of the pyrazoline C-4 stereocenter and two planar chiral subunits due to internal steric hindrance. The energy barriers of this steric hindrance were overcome in DMSO-d6 solutions at 60 C. The acetylation of some pyrazolyl-2-pyrazoline derivatives 2a-c,e helped to confirm the presence of the referred mixture of diastereomers.
TL;DR: In this article, a new porphyrin indolin-2-one conjugates were synthesized via palladium-catalyzed amination reactions of iodinated and dibrominated indolin 2-one derivatives with (2-amino-5,10,15,20,20-tetraphenylporphyrinato)nickel(II).
TL;DR: In this paper, a review of reaction chemistry and new ring synthetic methods for pyranones is presented, covering work published in the calendar year 2011, including new ring synthesis methods for trioxanes, tetraoxane, trithianes and oxathianes.
Abstract: The review covers work published in the calendar year 2011. Novel reaction chemistry and new ring synthetic methods for pyrans, [1]benzopyrans, dihydro[1]benzopyrans (chromenes, chromans), [2]benzopyrans, dihydro[2]benzopyrans (isochromenes, isochromans), pyranones, coumarins, chromones, xanthenes, xanthones, thiopyrans, dioxins, dioxanes, trioxanes, tetraoxanes, dithianes, trithianes, and oxathianes are reviewed.
TL;DR: Azomethine ylides generated in situ from the reaction of N-[2-, 3- and 4-(chromon-2-yl)phenyl]glycine and paraformaldehyde can be trapped with dipolarophiles in 1,3-dipolar cycloaddition reactions to yield flavone-nitrogen heterocycle dyads as mentioned in this paper.
TL;DR: The measurement of aryl-naphthyl rotational barriers in various solvents for two substituted 1,8-diarylnaphthalenes by dynamic (1)H NMR showed that ΔG(‡) trends in aromatic systems can be fully rationalized only when considering the different types of aromatic interactions.
Abstract: The measurement of aryl-naphthyl rotational barriers, ΔG⧧, in various solvents for two substituted 1,8-diarylnaphthalenes by dynamic 1H NMR showed that ΔG⧧ trends in aromatic systems can be fully rationalized only when considering the different types of aromatic interactions that can be established in the ground and transition states, namely, intramolecular interactions involving the aromatic rings and specific solvation interactions.
TL;DR: The Diels-Alder reaction of 2-styryl chromones with a pyrimidine ortho -quinodimethane was reported for the first time in this paper.
TL;DR: In this article, the separation and isolation of the four atropisomers of ortho-halogenated tetraarylporphyrins by semi-preparative HPLC is described.
Abstract: The separation and isolation of the four atropisomers of ortho-halogenated tetraarylporphyrins by semi-preparative HPLC is described. Full characterization and assignment of all 1H and 13C resonances of 5,10,15,20-tetrakis(2-fluoro or 2-chlorophenyl)porphyrins and 5,10,15,20-tetrakis(2-fluoro or chloro-5-N-ethylsulfamoylphenyl)porphyrins by 1D and 2D NMR techniques is reported. The outcome is an unequivocal evidence of the chlorosulfonation of meso-tetra(2-haloaryl)porphyrins on the 5′-position.