A study on design, virtual screening, and docking analysis of new ferulic acid analogs against the NF-kB therapeutic target

The human transcription factor NF-κB has an essential role in inflammatory responses and carcinogenesis. Ferulic acid (FA) is one of the plant phenolic compounds that shows therapeutic potential for anticancer, anti-diabetes, anti-aging, anti-inflammatory activities, etc. This study aims to develop novel FA-based NF-κB inhibitors. The docking study of FA analogs has revealed that FA74 (-7.3 kcal/mol), FA75 (-7.2 kcal/mol), and FA71 (-7.1 kcal/mol) are top NF-κB binders, in comparison with their parental compound, FA (-4.0 kcal/mol). Accordingly, FA74 establishes four hydrogen bonds with Arg 246 (p65), Gln 606 (p50), and Ser 546 (p50); FA75 and FA71 form three hydrogen bonds with Lys 541 (p50), Arg 246 (p65), and four hydrogen bonds with Arg 246 (p65), Lys 541 (p50), Ser 546 (p50) residues, respectively. FA forms four hydrogen bonds with Arg 33 (p65), Arg 187 (p65), and Gln 606 (p50) residues. The results suggest that FA analogs (FA74, FA75 & FA 71) show promising leads that may act as effective modulators of NF-κB activity through interaction with the p50 domain or p65 Nuclear Localising Sequence (NLS) or interference of gene expression. Further MD simulations, synthesis, and pre-clinical studies may elucidate the precise relationship between NF-κB and FA analogs. Słowa kluczowe: ferulic acid, NF-κB, docking, cancer, diabetes, inflammations