Abstract
The series of fifteen synthesized 4-hydroxycoumarin derivatives was subjected to antioxidant activity evaluation in vitro, through total antioxidant capacity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl radical, lipid peroxide scavenging and chelating activity. The highest activity was detected during the radicals scavenging, with 2b, 6b, 2c, and 4c noticed as the most active. The antioxidant activity was further quantified by the quantitative structure-activity relationships (QSAR) studies. For this purpose, the structures were optimized using Paramethric Method 6 (PM6) semi-empirical and Density Functional Theory (DFT) B3LYP methods. Bond dissociation enthalpies of coumarin 4-OH, Natural Bond Orbital (NBO) gained hybridization of the oxygen, acidity of the hydrogen atom and various molecular descriptors obtained, were correlated with biological activity, after which we designed 20 new antioxidant structures, using the most favorable structural motifs, with much improved predicted activity in vitro.
Highlights
Overall cell health depends on the balance between formation and elimination of free radicals [1].Free radicals, which originate both in normal or pathological metabolic transformations, host-defense against undesirable invasion, or host-response to a disturbance of the tissues’integrity, may begin chain reactions initiated mostly by reactive oxygen species (ROS) [1]
The structure potential of our derivatives was confirmed by structure-activity relationships (SAR), quantitative structure-activity relationships (QSAR) and Density Functional Theory (DFT) studies, which were used for the successful design of 20 novel improved coumarin antioxidant structures
In accordance with the results presented for the other activities (Sections 2.2–2.5), the total antioxidant capacity is presented as TAC50 values (Table 1) which are used in the QSAR study
Summary
Overall cell health depends on the balance between formation and elimination of free radicals [1]. Integrity (due to trauma, cellular damage, etc.), may begin chain reactions initiated mostly by reactive oxygen species (ROS) [1]. Superoxide anion (O2−) and hydroxyl radical (OH), in increased concentrations, can induce oxidative stress and cellular damage by altering the biological activities of lipids, proteins, DNA and carbohydrates [3], even to cellular death [1]. Due to the typical phenolic behavior [1] They act as potent metal chelators and free radical scavengers, resulting in a powerful antioxidant effect. Their antioxidant behavior could be applied in fat and oily foods to prevent oxidative deterioration, to replace known synthetic antioxidants. A coumarin derivative has to possess at least one hydroxy group [10]. The structure potential of our derivatives was confirmed by SAR, QSAR and Density Functional Theory (DFT) studies, which were used for the successful design of 20 novel improved coumarin antioxidant structures
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