Percorrer por autor "Ribeiro, Daniela"
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- 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathwaysPublication . Santos, Clementina M.M.; Ribeiro, Daniela; Silva, Artur; Fernandes, EduardaIn response to an inflammatory stimulus, arachidonic acid (AA), the main polyunsaturated fatty acid present in the phospholipid layer of cell membranes, is released and metabolized to a series of eicosanoids. These bioactive lipid mediators of inflammation arise physiologically through the action of the enzymes 5-lipoxygenase (5-LOX) and cyclooxygenases (constitutive COX-1 and inducible COX-2). It is believed that dual inhibition of 5-LOX and COXs may have a higher beneficial impact in the treatment of inflammatory disorders rather than the inhibition of each enzyme. With this demand for new dual-acting anti-inflammatory agents, a range of 2,3-diarylxanthones were tested through their ability to interact in the AA metabolism. In vitro anti-inflammatory activity was evaluated through the inhibition of 5-LOX-catalyzed leukotriene B4 (LTB4) formation in human neutrophils and inhibition of COX-1- and COX-2-catalyzed prostaglandin E2 (PGE2) formation in human whole blood. The results showed that some of the studied arylxanthones were able to prevent LTB4 production in human neutrophils, in a concentration-dependent manner. The xanthone with a 2-catechol was the most active one (IC50 ∼ 9 μM). The more effective arylxanthones in preventing COX-1-catalyzed PGE2 production presented IC50 values from 1 to 7 μM, exhibiting a structural feature with at least one non-substituted aryl group. All the studied arylxanthones were ineffective to prevent the formation of PGE2 catalyzed by COX-2, up to the maximum concentration of 100 μM. The ability of the tested 2,3-diarylxanthones to interact with both 5-LOX and COX-1 pathways constitutes an important step in the research of novel dual-acting anti-inflammatory drugs.
- 2,3-Diarylxanthones as strong scavengers of reactive oxygen and nitrogen species: a structure–activity relationship studyPublication . Santos, Clementina M.M.; Freitas, Marisa; Ribeiro, Daniela; Gomes, Ana Sara; Silva, Artur; Cavaleiro, José; Fernandes, EduardaXanthones are a class of oxygen-containing heterocyclic compounds widely distributed in nature. The natural derivatives can present different substitutions in the xanthone core that include hydroxyl, methoxyl, prenyl and glycosyl groups. The inclusion of aryl groups has only been reported for a few synthetic derivatives, the 2,3-diaryl moiety being recently introduced by our group. Xanthones are endowed with a broad spectrum of biological activities, many of them related to their antioxidant ability, including the scavenging of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as metal chelating effects. Considering the interesting and promising antioxidant activities present in compounds derived from the xanthone core, the main goal of this work was to evaluate the scavenging activity of the new 2,3-diarylxanthones for ROS, including superoxide radical (O2 ), hydrogen peroxide (H2O2), singlet oxygen (1O2), peroxyl radical (ROO ) and hypochlorous acid (HOCl), and RNS, including nitric oxide ( NO) and peroxynitrite anion (ONOO ). The obtained results revealed that the tested 2,3-diarylxanthones are endowed with outstanding ROS and RNS scavenging properties, considering the nanomolar to micromolar range of the IC50 values found. The xanthones with two catechol rings were the most potent scavengers of all tested ROS and RNS. In conclusion, the new 2,3-diarylxanthones are promising molecules to be used for their potential antioxidant properties.
- Arylxanthones with anti-inflammator potential in cellular systemsPublication . Santos, Clementina M.M.; Ribeiro, Daniela; Silva, Artur; Fernandes, EduardaXanthones are a family of naturally-occurring oxygenated heterocyclic compounds. A wide range of natural and synthetic analogues are known to possess diverse biological activities including antifungal, antimalarial, antioxidant and antitumor, among others [1]. There are only a few publications related to arylxanthones [2], most of them focused on arylxanthones synthetic strategies and their biomedical potential, mainly highlighting them as effective scavengers of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [3,4]. As far as we know, the anti-inflammatory potential of xanthones bearing an aryl group has not been studied so far. With this idea in mind, our purpose was to evaluate the putative anti-inflammatory effects of several arylxanthones bearing hydroxyl groups in certain positions of their main core, namely through their ability to inhibit 5-lipoxygenase (5-LOX) and cyclooxygenase 1 (COX-1) and 2 (COX-2), both enzymes involved in the arachidonic acid metabolism [5,6]. Preliminary results showed that some of the studied arylxanthones were able to prevent leukotriene B4 production in human neutrophils, the xanthone with a catechol group at position 2 being the most active one. The inhibition of prostaglandin E2 production was assessed in human whole blood and the majority of the tested compounds were able to inhibit COX-1 while being completely ineffective in COX-2.
- Design, synthesis and preliminar antioxidant evaluation of new hydroxy- chromone and xanthone derivativesPublication . Albuquerque, Hélio; Proença, Carina; Ribeiro, Daniela; Freitas, Marisa; Santos, Clementina M.M.; Fernandes, Eduarda; Silva, ArturChromone and xanthone derivativas are well-known for their outstanding antioxidant properties. ln an effort to develop new antioxidants with improved efficacy, here we cteveloped a new synthetic strategy to prepare hydroxylated chromones 3 and xanthones 4 with extended conjugated rr-systems. The synthetic strategy involved the aldolcondensation of 2-methylchromones 1 with cinnamaldehyde 2 to give chromones 3. Subsequent electrocyclization and oxidation of chromones 3 afforded xanthones 4 (Fig. 1 ). The scavenging activities of both derivativas 3 and 4 were addressed against both reactive oxygen species (ROS) and reactive nitrogen species (RNS). Ali tested compounds exhibited scavenger effects dependent on the concentration, with ICso values found in the micromolar range [1].
- Inhibition of NF-kB activation and cytokines production in THP-1 monocytes by 2-styrylchromonesPublication . Gomes, Ana Sara; Capela, João Paulo; Ribeiro, Daniela; Freitas, Marisa; Silva, Artur; Pinto, Diana; Santos, Clementina M.M.; Cavaleiro, José; Lima, José L.F.C.; Fernandes, EduardaNuclear factor kappa B (NF-kB) is one of the most important transcription factors whose modulation triggers a cascade of signaling events, namely the expression of many cytokines, enzymes, chemokines, and adhesion molecules, some of which being potential key targets for intervention in the treatment of inflammatory conditions. The 2-styrylchromones (2-SC) designation represents a well-recognized group of natural and synthetic chromones, vinylogues of flavones (2-phenylchromones). Several 2-SC were recently tested for their anti-inflammatory potential, regarding the arachidonic acid metabolic cascade, showing some motivating results. In addition, several flavones with structural similarities to 2-SC have shown NF-kB inhibitory properties. Hence, the aim of the present work was to continue the investigation on the interference of 2-SC in inflammatory pathways. Herein we report their effects on lipopolysaccharide (LPS)-induced NF-kB activation and consequent production of proinflammatory cytokines/chemokine, using a human monocytic cell line (THP-1). From the twelve 2-SC tested, three of them were able to significantly inhibit the NF-kB activation and to reduce the production of the proinflammatory cytokines/chemokine. The compound 3',4',5-trihydroxy-2- styrylchromone stood up as the most active in both assays, being a promising candidate for an anti-inflammatory drug.
- NDPO2 as a selective generator of 1o2 used in the scavenging activity assay of 2,3-diarylxanthonesPublication . Santos, Clementina M.M.; Freitas, Marisa; Ribeiro, Daniela; Gomes, Ana Sara; Silva, Artur; Cavaleiro, José; Fernandes, Eduarda
- Novel chromone and xanthone derivatives: synthesis and ROS/RNS scavenging activitiesPublication . Proença, Carina; Albuquerque, Hélio; Ribeiro, Daniela; Freitas, Marisa; Santos, Clementina M.M.; Silva, Artur; Fernandes, EduardaChromones and xanthones are oxygen-containing heterocyclic compounds acknowledged by their antioxidant properties. In an effort to develop novel agents with improved activity, a series of compounds belonging to these chemical classes were prepared. Their syntheses involve the condensation of appropriate 2-methyl-4H-chromen-4-ones, obtained via Baker-Venkataraman rearrangement, with (E)-3-(3,4-dimethoxyphenyl)acrylaldehyde to provide the corresponding 2-[(1E,3E)-4-(3,4-dimethoxyphenyl)buta-1,3-dien-1-yl]-4H-chromen-4-ones. Subsequent electrocyclization and oxidation of these compounds led to the synthesis of 1-aryl-9H-xanthen-9-ones. After cleavage of the protecting groups, hydroxylated chromones and xanthones were assessed as scavenging agents against both reactive oxygen species (ROS) [superoxide radical (O2(•-)), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen ((1)O2), and peroxyl radical (ROO(•))] and reactive nitrogen species (RNS) [nitric oxide ((•)NO) and peroxynitrite anion (ONOO(-))]. Generally, all the tested new hydroxylated chromones and xanthones exhibited scavenger effects dependent on the concentration, with IC50 values found in the micromolar range. Some of them were shown to have improved scavenging activity when compared with previously reported analogues, allowing the inference of preliminary conclusions on the structure-activity relationship.
- ROS and RNS Scavenging Activity by 2,3-DiarylxanthonesPublication . Santos, Clementina M.M.; Freitas, Marisa; Ribeiro, Daniela; Gomes, Ana Sara; Silva, Artur; Cavaleiro, José; Fernandes, EduardaXanthones constitute an important class of heterocyclic compounds that commonly occur in nature. The inclusion of aryl groups has only been reported for a few synthetic derivatives, being the 2,3-diaryl moiety recently introduced by our group.~ The pharmacological properties of both natural and synthetic xanthones have attracted great attention namely as antioxidant, anti-allergic, anti-inflammatory, antimalarial and antitumour protectors. The antioxidant activity deserves special mention, considering the potent scavenging activity for reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as metal chelating activity already reported for some compounds bearing the xanthone scaffold. Thus, the main goal of this work was to evaluate the putative scavenging effect on NO, ONOO- and O2 - of the new synthetic 2,3-diarylxanthones (Figure 1), using in vitro non-cellular systems
- A study towards drug discovery for the management of type 2 diabetes: Mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivativesPublication . Rocha, Sónia; Sousa, Adelaide; Ribeiro, Daniela; Correia, Catarina M.; Silva, Vera L.M.; Santos, Clementina; Silva, Artur; Araújo, Alberto N.; Fernandes, Eduarda; Freitas, MarisaThe inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, is one of the major therapeutic strategies for the treatment of type 2 diabetes mellitus. Chalcones have been recognized for their multiple biological activities, including antidiabetic properties, through unclear mechanisms. In the present work, a panel of chalcones bearing hydroxy, methoxy, methyl, nitro, chloro, fluoro and bromo substituents were evaluated against α-amylase and α-glucosidase activities, most of them for the first time. The results showed that the substitution patterns and the type of substituents of chalcones influence their inhibitory activity. The presence of hydroxy groups at C-2’- and C-4’ of the A ring and at C-3 and C-4 of the B ring favors the intended effect. Chalcones holding nitro groups and chloro substituents, together with a hydroxy group in the chalcone scaffold, showed strong inhibition of the α-glucosidase activity. The present study provides related scaffolds that may serve as the basis for the design and synthesis of new structures in order to obtain the ideal antidiabetic chalcone.
- The antioxidant activity of novel chromones and xanthones: a structure-activity relationshipPublication . Proença, Carina; Ribeiro, Daniela; Freitas, Marisa; Albuquerque, Hélio; Santos, Clementina M.M.; Silva, Artur; Fernandes, EduardaChromones and xanthones are oxygen-containing heterocyclic compounds with bioactive properties widely reported in the literature, specially concerning to their antioxidant properties. The search for new natural and synthetic chromone and xanthone derivatives order to evaluate and discover new structural features rendering optimized biological effects has been a challenge. Thus, the aim of this work was to evaluate the scavenging activity of reactive oxygen (ROS) and nitrogen (RNS) species of new synthetic hydroxylated chromones and xanthones (Fig. 1) using in vitro non-cellular systems. These compounds exhibited scavenger effects dependent on the concentration, with IC50 values found at the micromolar range. The overall scavenging activity of chromones was better than xanthones, specially the one of chromone 3A. In conclusion, the novel tested chromone and xanthone scaffolds proved to be promising pharmacophores with potential therapeutic applications as antioxidant agents.