2-Styrylchromones: Novel strong scavengers of reactive oxygen and nitrogen species

Abstract

Abstract-2-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, IC 50 s 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.

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

“…Generally, the compounds were shown to be equally potent scavengers in the absence and presence of NaHCO 3 , with the exception of xanthones 13a (more active in the presence of NaHCO 3 ) and 13c (more active in the absence of NaHCO 3 ). A similar conclusion can be drawn from the scavenging effects presented by several phenolic compounds and flavonoids [29,33,34]. Chromone 12c proved to be the most active derivative, with IC 50 of 0.29 ± 0.02 and 0.30 ± 0.04 mM, in the absence and in the presence of NaHCO 3 25 mM, respectively (Table 3).…”

“…The results indicate that chromone 12c (1.63 ± 0.09) has higher scavenging effect, followed by chromones 12a (1.44 ± 0.01) and 12b (1.40 ± 0.05), with similar ORAC values. Considering that chromones 12a-12c are less active than the 2-styrylchromones studied by Gomes et al we can conclude that the additional double bond at C-2 decreases the scavenging effect against this ROS [29]. Analysing the results of xanthones, compounds 13a (1.5 ± 0.1) and 13c (1.58 ± 0.09) are the most active ones, followed by compound 13b (1.1 ± 0.1).…”

“…The absence of OH groups in the A-ring of chromones increases the scavenging activity against NO when compared to its presence in position 5 or 7, being more effective in the former case. Chromones 12a-12c were much weaker scavengers than the structurally related 2-styrylchromones tested by Gomes et al, indicating that the introduction of a double bond at C-2 decreases the scavenging capacity [29]. With respect to xanthone derivatives, the more active was compound 13c followed by compound 13b (IC 50 1.5 ± 0.1 mM) and compound 13a (IC 50 1.99 ± 0.09 mM).…”

“…Analysing the results we can conclude that chromones 12a-12c were shown to be more effective scavengers of 1 O 2 than the 2-styrylchromones and flavones with comparable structures [29], indicating that the additional double bonds at C-2 of the chromone moiety clearly influence the scavenger effect, increasing its activity. Another important feature is the presence of the 5-OH group to improve the 1 O 2 scavenging potential in contrast to their substitution at C-7 that brings no advantage [29]. In what concerns to xanthones, the absence of OH groups in B-ring increases 1 O 2 scavenging activity when compared to its presence at C-6 or C-8 of the xanthone backbone, the 6-OH derivative (13c) being more active than the 8-OH derivative (13b).…”

“…The importance of these OH groups on the A-ring were previously reported for the HOCl scavenging activity of flavones (analogues of chromones 12a-12c without the 1,3-diene system) and 2-styrylchromones (analogues of chromones 12a-12c lacking one double bond), related to the ability to promote the chlorination at C-6 and C-8 positions, via an electrophilic aromatic substitution [28]. On the other hand, the additional double bond found in the new chromones seems to be unfavourable for the HOCl scavenging activity since these compounds were less potent scavengers than the previously tested 2-styrylchromones [29]. 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).…”