Browsing by Author "Gomes, Ana Sara"
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- 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.
- 2-Styrylchromones: novel strong scavengers of reactive oxygen and nitrogen speciesPublication . Gomes, Ana Sara; Fernandes, Eduarda; Silva, Artur; Pinto, Diana; Santos, Clementina M.M.; Cavaleiro, José; Lima, José Costa2-Styrylchromones are a small group of naturally occurring chromones, vinylogues of flavones (2-phenylchromones). Natural and synthetic 2-styrylchromones have been tested in different biological systems, showing activities with potential therapeutic applications. In particular, the potential and hitherto understudied antioxidant behavior of these compounds has been raised as a matter of interest. Thus the present work consisted in the study of the in vitro scavenging activities for reactive oxygen species (ROS) and reactive nitrogen species (RNS) of various 2-styrylchromone derivatives and structurally similar flavonoids. Some of the studied 2-styrylchromones proved to be extremely efficient scavengers of the different ROS and RNS, showing, in some cases, IC50s under 1 lM. The hydroxylation pattern of 2-styrylchromones, especially in the B-ring but also in the A ring, modulates the activity of these compounds, the catecholic derivatives being the most effective scavengers. The styryl pattern also contributes to their observed outstanding antioxidant activity. In conclusion, the scavenging activities for ROS/RNS of 2-styrylchromone derivatives, here shown for the first time, provide novel and most promising compounds to be applied as antioxidants.
- Anti-inflammatory potencial of 2-Styrylchromones regarding their interference with arachidonic acid metabolic pathwaysPublication . Gomes, Ana Sara; Fernandes, Eduarda; Silva, Artur; Santos, Clementina M.M.; Pinto, Diana; Cavaleiro, José; Lima, José Costa
- Anti-inflammatory potential of 2-styrylchromones regarding their interference with arachidonic acid metabolic pathwaysPublication . Gomes, Ana Sara; Fernandes, Eduarda; Silva, Artur; Pinto, Diana; Santos, Clementina M.M.; Cavaleiro, José; Lima, José CostaCyclooxygenases (COXs) are the key enzymes in the biosynthesis of prostanoids. COX-1 is a constitutive enzyme while the expression of COX-2 is highly stimulated in the event of inflammatory processes, leading to the production of large amounts of prostaglandins (PGs), in particular PGE2 and PGI2, which are pro-inflammatory mediators. Lipoxygenases (LOXs) are enzymes that produce hydroxy acids and leukotrienes (LTs). 5-LOX metabolizes arachidonic acid to yield, among other products, LTB4, a potent chemoattractantmediator of inflammation. The aim of the present work was to evaluate the anti-inflammatory potential of 2-styrylchromones (2-SC), a chemical family of oxygen heterocyclic compounds, vinylogues of flavones (2-phenylchromones), by studying their COX-1 and COX-2 inhibitory capacity as well as their effects on the LTB4 production by stimulated human polymorphonuclear leukocytes (PMNL). Some of the tested 2-SC were able to inhibit both COX-1 activity and LTB4 production which makes them dual inhibitors of the COX and 5-LOX pathways. The most effective compounds in this study were those having structural moieties with proved antioxidant activity (30,40-catechol and 40-phenol substituted B-rings). This type of compounds may exhibit anti-inflammatory activity with a wider spectrum than that of classical non-steroidal anti-inflammatory drugs (NSAIDs) by inhibiting 5-LOX product-mediated inflammatory reactions, towards which NSAIDs are ineffective.
- Cyclic voltammetric analysis of 2-styrylchromonesPublication . Gomes, Ana Sara; Fernandes, Eduarda; Garcia, M. Beatriz; Silva, Artur; Pinto, Diana; Santos, Clementina M.M.; Cavaleiro, José; Lima, José Costa
- Cyclic voltammetric analysis of 2-styrylchromones: Relationship with the antioxidant activityPublication . Gomes, Ana Sara; Fernandes, Eduarda; Garcia, M. Beatriz; Silva, Artur; Pinto, Diana; Santos, Clementina M.M.; Cavaleiro, José; Lima, José Costa2-Styrylchromones (2-SC) are a chemical family of oxygen heterocyclic compounds, vinylogues of flavones (2-phenylchromones), whose occurrence in nature has been reported. Recently, several 2-SC derivatives were demonstrated to have antioxidant properties, namely, xanthine oxidase inhibition, hepatoprotection against pro-oxidant agents in cellular and non-cellular systems and scavenging activity against reactive oxygen and reactive nitrogen species (ROS and RNS). Considering these antioxidant properties, it may be hypothesised that the electrochemical redox behaviour of 2-SC contributes significantly to their activity. To test this hypothesis, the electrochemical behaviour of different 2-SC was studied, together with a number of flavonoids with well-known antioxidant activities, by cyclic voltammetry, and the results correlated to their ability to scavenge ROS and RNS. The results obtained showed that 2-SC with a catecholic B-ring have a low oxidation peak potential corresponding to the oxidation of the 30,40-OH (catechol) moiety. The compounds with a phenolic B-ring have a common peak, with oxidation potential values of about +0.4/+0.5 V versus Ag/AgCl, corresponding to the oxidation of the 40-OH. The oxidation of the hydroxyl substituents in the A-ring generated peaks of higher potentials (+0.7/+0.8 V vs Ag/AgCl). The results from the scavenging assays were in agreement with those obtained from the cyclic voltammetry, that is, higher scavenging effects corresponded to lower values of oxidation potentials, with significant correlation coefficients. The values obtained for the studied flavonoids are in accordance with the literature, and reflect their relative antioxidant activity, when compared to the studied 2-SC. Thus, in this family of compounds, oxidation potentials obtained by cyclic voltammetry seem to be applicable as a general indicator of radical scavenging activity.
- Inhibition of Leukotriene B4 production in human Neutrophils by 2-StyrylchromonesPublication . Gomes, Ana Sara; Fernandes, Eduarda; Freitas, Marisa; Silva, Artur; Santos, Clementina M.M.; Pinto, Diana; Cavaleiro, José; Lima, José Costa
- 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.
- Interactions of 2-Styrylchromones with pro-inflamatory enzymes and oxidative speciesPublication . Gomes, Ana Sara; Fernandes, Eduarda; Silva, Artur; Santos, Clementina M.M.; Pinto, Diana; Cavaleiro, José; Lima, José Costa
- Metodologias para avaliar a actividade captadora de espécies reactivas de oxigénio e de azoto envolvidas no processo inflamatórioPublication . Gomes, Ana Sara; Silva, Artur; Pinto, Diana; Santos, Clementina M.M.; Cavaleiro, José; Fernandes, Eduarda; Lima, José CostaAs espécies reactivas de oxigénio (ERO) e de azoto (ERA) estão envolvidas nos processos inflamatórios, nomeadamente através da sua produção c libertação pelos neutrófilos. Apesar da produção dessas espécies fazer pal1e dos mecanismos de defesa inata do organismo, por vezes esta torna-se descontrolada, com efeitos deletérios para os tecidos. Na verdade, foi já sugerido em diferentes estudos que a actividade anti-inflamatória de fármacos da classe dos anti-inflamatórios não esteróides se deve, cm parte, à sua capacidade de interferir nas reacções mediadas por ERO e ERA. Assim sendo, o desenvolvimento e aplicação de métodos que pe1111itam avaliar a actividade captadora destas espécies assume um importante papel no estudo de novas moléculas com potencial anti-inflamatório.