Multitarget Mechanisms of 5‐hydroxy Ferulic Acid for Cancer Prevention: A Computational Chemistry Study

Abstract

AbstractThis study used computational methods to investigate the multitarget mechanisms of 5‐hydroxy ferulic acid in preventing cancer. The antiradical activity of 5‐hydroxy ferulic acid was systematically studied by using the M06‐2X/6‐311++G(d,p) method in both pentyl ethanoate (lipid‐like) and water media. The results show that 5‐hydroxy ferulic acid is more effective at scavenging the HOO• radical (koverall=5.2×108 M−1s−1) than Trolox (koverall=1.3×105 M−1s−1) in aqueous solution. The complexation ability of 5‐hydroxy ferulic acid with Cu(II) ions was investigated at the M06/6‐311++G(d,p) level of theory under physiological pH conditions. The most thermodynamically stable complexes can slow down about 107 times the Haber‐Weiss cycle's first reaction (from 4.2×109 M−1s−1 to 3.8×102 M−1s−1) and mitigate the potential damage caused by ⋅OH radical production. Furthermore, by performing molecular docking simulations on protein‐ligand adducts and comparing their activity to that of 5‐fluorouracil (a commercial anticancer drug), the existing forms of 5‐hydroxy ferulic acid at physiological pH were extremely effective at inhibiting the thymidylate synthase enzyme. Based on these findings, 5‐hydroxy ferulic acid may be an effective cancer treatment.