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

This 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= 5.2x108 M 1s 1) than Trolox (koverall= 1.3x105 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 HaberWeiss cycle's first reaction (from 4.2x109 M 1s 1 to 3.8x 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.

Automated summary

This study used computational methods to investigate the multitarget mechanisms of 5-hydroxy ferulic acid in preventing cancer. The results showed that 5-hydroxy ferulic acid has strong antiradical activity and can form stable complexes with Cu(II) ions. It also exhibited effective inhibition of the thymidylate synthase enzyme. Based on these findings, 5-hydroxy ferulic acid may be a promising cancer treatment.