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  • Most human diseases e g cancer

    2024-04-15

    Most human diseases (e.g., cancer, diabetes, and neurodegenerative diseases) are complex and multifactorial. Several investigations in the literature focused on new multi-target drug development, which implies active pharmacophores incorporation in one scaffold (Meunier, 2008, Lazar et al., 2004, Teiten et al., 2014). New hybrids have been successfully tested and proposed, such as potential drug candidates, e.g., quinoline and trioxaquine derivatives against malaria (Kouznetsov and Gómez-Barrio, 2009, Chauhan et al., 2010), mustard derivatives that are designed to be similar to anticancer drugs (Xu et al., 2014) and nano-hybrid structures for drug delivery improvement (Allen et al., 2015). Sandhu et al., 2014, describe several examples of hybrid coumarin derivatives with multifunctional characteristics to improve their therapeutic profile. Another study reports stilbene-coumarin synthetic structures that were assayed towards tumoral activity (Belluti et al., 2010). Vázquez-Rodríguez et al., 2013, described a coumarin-chalcone hybrid synthesis with better antioxidant properties than catechin, quercetin and simple coumarin skeleton. Similarly, Matos et al., 2015, synthesized new coumarin-resveratrol compounds with an interesting antioxidant profile towards oxygen reactive species. Furthermore, these compounds can reduce the ROS (reactive oxygen species) generation in RAW 264.7 cells. These facts prompted us to design a synthetic route of coumarin functionalized scaffold with hydroxyl benzoic acids (known antioxidant frameworks (Kakkar and Bais, 2014, Wojdyło et al., 2007, Li et al., 2011) and perform different antioxidant assays to study new derivative antioxidant properties.
    Experimental section
    Results and discussion
    Conclusions In non-biological assays, the inclusion of polyphenolic structures into coumarin improves the antioxidant capacity compared to the 1a scaffold. A synergy phenomenon was observed in BAY 61-3606 3c for FRAP and ORAC assays and compound 3b in the assay of superoxide anion scavenging. In the ESR experiments, we found that all compounds could compete with spin trap to scavenge OH, which implies that the compounds are potential candidates to reduce the hydroxyl-radical-induced oxidative damage. The superoxide scavenging results show that compound 3b is the best molecule of the entire series with an AI50 of 0.064mM. As expected, there is no correlation among the obtained values using different methodologies because of different oxygen reactive specie (with different reactivity) in each antioxidant assay and medium. In this study, we obtained compounds with better antioxidant capacity than the starter coumarin. Every proposed substitution has better antioxidant activity than the coumarin precursor 1a. Considering the results in simple biological experiments, new derivatives can exert their antioxidant capacity at the biological level (lipophilic media). Nevertheless, the correlation of logD vs CAA shows that the lipophilicity is not the only factor in the compound behaviour. For our compounds, an encapsulation method can be interesting to attempt. From the theoretical calculations (Fukui index and BDE), we can discriminate different reactive sites in the new molecules where the oxidative process occurs. We found a correlation between both methods: in compound 3a, the most reactive region in the molecule was the caffeic acid moiety, whereas in compounds 3b and 3c, the coumarin scaffold was the active site.
    Introduction An increasing interest for food antioxidants has arisen over the last two decades due to growing evidence of their health-promoting effects. In this respect, a more integrated information about putative beneficial effects of food antioxidants may derive from integration of in vitro assessment of Antioxidant Capacity (AC) of foods with ex vivo measurement of serum/plasma/blood antioxidant status after food consumption (Soccio, Laus, Alfarano, & Pastore, 2016). Blood antioxidant status considers implicitly bioavailability and metabolism of antioxidants; moreover, it plays a prominent role in maintaining cellular redox homeostasis (Davies, 1995, Halliwell and Cross, 1994) and in preserving endothelial function, essential for an healthy aging (El Assar, Angulo, & Rodríguez-Mañas, 2013).