Computational and experimental validation of antioxidant properties of synthesized bioactive ferulic acid derivatives

Abstract

Ferulic acid, a well-known natural phenolic compound, is considerably reported for its hydroxyl and peroxyl radical scavenging activities. However, the antioxidant capacity of ferulic acid is limited by its relatively low solubility in hydrophobic media thereby preventing its application for autoxidation of fats and oils. To this end, several research efforts are being made to maximize the therapeutic benefits of ferulic acid and these efforts included but not limited to structural modification of ferulic acid to produce its derivatives. In this study, we synthesized ester and amide derivatives of ferulic acid and evaluated them for in vitro antioxidant potential as well as molecular docking properties. Data revealed that ferulic ester and amide derivatives had excellent antioxidant capacity and demonstrated strong inhibitory potential. Analysis of molecular docking indicated ferulic ester as potent inhibitor of target proteins in breast cancer as well as in oxidative stress. Taken together, the findings support potent antioxidant properties by these ferulic derivatives. Findings may become relevant where structural modification to enhance physico-chemical properties without compromising the antioxidant and/or medicinal potential are desirable.

Synthesis, Photoisomerization, Antioxidant Activity, and Lipid-Lowering Effect of Ferulic Acid and Feruloyl Amides

“…Clearly, the RSA(1) values are slightly lower for t-FEF77. This result is consistent with previous studies, where it has been shown that FA was more effective than the urethane amide derivative [9] or a tyrosine-amide derivative [18] in scavenging DPPH radicals. Since the lower antioxidant efficiency of monophenol rings has been well established in literature [19,20], we decided to carry out the experiments for a longer time, in order to evaluate the contribution of the additional monophenolic groups present in FEF77.…”

“…FA contains a methoxy group and a propenoic acid moiety at the ortho and para positions of phenol, respectively. The electron-donating methoxy group might be responsible for the increased antioxidant activity of FA with respect to 4-hydroxycinnamic acid, while the E double bond of the propenoic group might play a responsible role in the stabilization of the phenoxyl radical by resonance [ 9 ]. Although several natural phenols containing a catechol, or a pyrogallol type rings, present high radical scavenging activity in vitro, their high susceptibility to oxidation makes their half-life in the body strongly reduced and therefore their applicability as active pharmaceutical ingredients limited [ 10 , 11 ].…”

“…However, FA suffers a relatively low solubility in hydrophobic media, which limits its ability to cross lipid-rich cell membranes and its application as an inhibitor of lipids and fats autoxidation [ 9 ]. For this reason, the synthesis of feruloyl derivatives with antioxidant activity and physicochemical tuned properties is highly desirable.…”

Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium‐induced oxidative challenge, inflammation, and apoptosis in rats

“…The antioxidant capacity of FA is enabled by its hydroxy and phenoxy groups, which can directly scavenge O 2 ‐ , HO·, and H 2 O 2 via a one electron transfer reaction (Hasanein et al., 2018). Also, unsaturated double bond in the structure of FA can offer an additional protection for cell membrane against harmful ROS (Adeyemi et al., 2018).…”

Comparative evaluation of the antioxidant capacity of ferulic acid and synthesized propionyl ferulate

“…In addition, the demand for antioxidants in various manufacturing processes, particularly the food industry, has been on the increase, leading to the production of synthetic antioxidants to match this demand. However, in recent years, there has been a shift from synthetic to natural antioxidants (Adeyemi et al, 2018). The preference for the use of natural antioxidants stems from the belief that they have lower toxicity than their synthetic counterparts.…”