2,3-Diarylxanthones as strong scavengers of reactive oxygen and nitrogen species: A structure–activity relationship study

Abstract

a b s t r a c tXanthones 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 (O 2 ÁÀ ), hydrogen peroxide (H 2 O 2 ), singlet oxygen ( 1 O 2 ), peroxyl radical (ROO Å ) and hypochlorous acid (HOCl), and RNS, including nitric oxide ( Å NO) and peroxynitrite anion (ONOO À ). 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 IC 50 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.

Novel chromone and xanthone derivatives: Synthesis and ROS/RNS scavenging activities

“…This comes in agreement with previous studies on flavonoids that the strong intramolecular hydrogen bond between the OH group peri to the carbonyl group is generally disadvantageous for the scavenging activity of these compounds [23]. In addition, the new 1-arylxanthones 13a-13c were less potent scavengers than other xanthones possessing a catechol group at position 2 or 3 of their skeleton [24]. It was not possible to determine the scavenging effect of chromones 12a and 12b due to the precipitation that occurred in the tested system.…”

“…An interesting feature common to all the ROS described is the fact that 6-OH xanthone 13c was shown to have improved scavenging activity when compared to the 8-OH xanthone 13b. Similar to the H 2 O 2 scavenging assays, the ROO scavenging effects of the tested 1-arylxanthones showed to be more efficient than the 2,3-diarylxanthones studied by Santos et al [24]. In fact, they concluded that, unlike to the observed for the other ROS, the introduction of phenolic groups at C-2 or C-3 of the xanthone core is more favourable for the scavenging of ROO that the addition of catechol groups in these positions.…”

“…Similarly to the above described for the scavenging effect against H 2 O 2 , the 6-OH substitution (compound 13c, IC 50 31 ± 3 mM) in the tested xanthones favoured the scavenging of HOCl in comparison to the 8-OH derivative (compound 13b, IC 50 96 ± 8 mM) or even their absence in the main core (compound 13a, IC 50 158 ± 18 mM). The 2,3-diarylxanthones already reported were found to be more active than the tested 1-arylxanthones, suggesting the importance of the catechol group at C-2 or C-3 rather than in C-1 to their reaction with this ROS [24].…”

“…However, their presence at C-6 (compound 13c, IC 50 518 ± 26 mM) seems to have a positive effect for the H 2 O 2 scavenging effect in comparison to its presence at C-8 (compound 13b, IC 50 658 ± 23 mM). The study developed by Santos et al [24] showed that xanthones possessing catechol groups at positions 2 or 3 of the xanthone backbone have no effect in preventing the oxidation of lucigenin promoted by H 2 O 2 . Taking into consideration that these xanthones have no OH groups in B-ring, we can infer that their inclusion appears to be important to enhance the scavenging properties against this ROS.…”

2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways

“…Aryl groups linked to xanthones are scarce in natural sources, but several publications reporting their synthesis and/or biomedical potential have been highlighted in literature and reviewed in [13]. In fact, the hydroxylated 2,3-diarylxanthones studied in the present work were already described as capable of scavenging oxygen and nitrogen reactive species [14,15] and inhibiting lipid peroxidation [16]. As so, they can be seen as excellent candidates to act as modulators of the inflammatory process.…”