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

Ibtisam Khan Mayana; Srinivasulu Cheemanapalli; Lavanya Thopireddy; Suresh Yarrappagaari; Sobha Rani Tenkayala; S.N. Krushna Naik; Ambedkar Yarrapalle; Rajeswara Reddy Saddala

doi:10.12923/cipms-2025-0016

Authors

Ibtisam Khan Mayana Division of Ethnopharmacology, Department of Biotechnology, School of Herbal Studies and Naturo Sciences, Dravidian University, Kuppam, India Author https://orcid.org/0009-0005-4460-7554
Srinivasulu Cheemanapalli Department of Botany, Regional Ayurveda Research Institute, Itanagar, India Author https://orcid.org/0000-0002-5377-2835
Lavanya Thopireddy Department of Zoology, KVR Government College for Women, Cluster University, Kurnool, India Author https://orcid.org/0000-0003-4814-6802
Suresh Yarrappagaari Division of Ethnopharmacology, Department of Biotechnology, School of Herbal Studies and Naturo Sciences, Dravidian University, Kuppam, India Author https://orcid.org/0009-0008-6649-3510
Sobha Rani Tenkayala Department of Chemistry, School of Herbal Studies and Naturo Sciences, Dravidian University, Kuppam, India Author https://orcid.org/0000-0002-5085-1394
S.N. Krushna Naik Department of Biochemistry, Sri Krishnadevaraya University, Anantapuramu, India Author https://orcid.org/0000-0003-0385-6819
Ambedkar Yarrapalle Department of Biotechnology, Yogi Vemana University, India Author https://orcid.org/0009-0007-8879-3779
Rajeswara Reddy Saddala Division of Ethnopharmacology, Department of Biotechnology, School of Herbal Studies and Naturo Sciences, Dravidian University, Kuppam, India Author https://orcid.org/0000-0001-8474-0791

DOI:

https://doi.org/10.12923/cipms-2025-0016

Keywords:

ferulic acid, NF-κB, docking, cancer, diabetes, inflammations

Abstract

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.

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

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