Computational Profile of Novel Natural Bioactive Inhibitors of NF-κB

Computational Profile of Novel Natural Bioactive Inhibitors


  • Muhammad Ishaq Department of Zoology, University of Education, Lahore, Pakistan
  • Muhammad Mansha Department of Zoology, University of Education, Lahore, Pakistan
  • Muhammad Faisal Maqbool Cancer Research Lab, Department of Zoology, University of the Punjab, Lahore, Pakistan
  • Muhammad Khan Cancer Research Lab, Department of Zoology, University of the Punjab, Lahore, Pakistan
  • Azeem Saeed Allama Iqbal Medical College, Lahore, Pakistan



NF-κB, Anti-Cancer, Inflammation


Nuclear factor-κB (NF-κB) represents a family of inducible transcription factors, which regulates a large array of genes involved in different processes of the immune and inflammatory responses. Deregulated NF-κB activation contributes to the pathogenic process of various diseases such as inflammation and cancer. NF-κB signaling in cancer cells is involved in cellular proliferation, angiogenesis, invasion, metastasis, development of drug resistance and anti-apoptosis. Objective: To identify potent NF-κB and IκBα inhibitors using molecular docking study. Methods: Proteins and ligands were prepared from Pymol and AutoDock vina and results were visualized by using Discovery studio visualizer. Results: Natural bioactive compounds such as Brevilin A, Tagitinin E, Japonicone G and Hiyodorilactone A were targeted on NF-κB and IκBα. The docking score of the Brevilin A, Tagitinin E, Japonicone G and Hiyodorilactone A with NF-κB were -9.8Kcal/mol, -10.1Kcal/mol, -11.9Kcal/mol, and - 8.4Kcal/mol respectively. The docking score of the Brevilin A, Tagitinin E, Japonicone G and Hiyodorilactone A with IκBα were -7.1Kcal/mol, -7.0Kcal/mol, -8.8Kcal/mol and -6.8Kcal/mol respectively. Control group (JSH-23 synthetic inhibitor) showed -6.5Kcal/mol and -5.5Kcal/mol with NF-κB and IκBα respectively. Conclusions: The present study reflects that Brevilin A, Tagitinin E, Japonicone G and Hiyodorilactone A show promising results as a crucial drug target in NF-κB signaling cascade. However, to validate the inhibitory activity of these ligands further in-vitro analysis are suggested to develop novel anti-inflammatory/anti-cancer drugs.


Pai P and Sukumar S. HOX genes and the NF-κB pathway: a convergence of developmental biology, inflammation and cancer biology. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2020 Dec; 1874(2): 188450. doi: 10.1016/j.bbcan.2020.188450.

Zhang Q, Lenardo MJ, Baltimore D. 30 years of NF-κB: a blossoming of relevance to human pathobiology. Cell. 2017 Jan; 168(1):3 7-57. doi: 10.1016/j.cell.2016.12.012.

Das R, Mehta DK, Dhanawat M. Medicinal plants in cancer treatment: Contribution of nuclear factor-kappa B (NF-kB) inhibitors. Mini Reviews in Medicinal Chemistry. 2022 Aug; 22(15): 1938-62. doi: 10.2174/1389557522666220307170126.

Lin Y, Bai L, Chen W, Xu S. The NF-κB activation pathways, emerging molecular targets for cancer prevention and therapy. Expert opinion on therapeutic targets. 2010 Jan; 14(1): 45-55. doi: 10.1517/14728220903431069.

Capece D, Verzella D, Flati I, Arboretto P, Cornice J, Franzoso G. NF-κB: Blending metabolism, immunity, and inflammation. Trends in Immunology. 2022 Sep; 43(9): 757-75. doi: 10.1016/

Jimi E, Huang F, Nakatomi C. NF-κB signaling regulates physiological and pathological chondrogenesis. International Journal of Molecular Sciences. 2019 Dec; 20(24): 6275. doi: 10.3390/ijms20246275.

Zheng C, Yin Q, Wu H. Structural studies of NF-κB signaling. Cell research. 2011 Jan; 21(1): 183-95. doi: 10.1038/cr.2010.171.

Kanzaki H, Chatterjee A, Hossein Nejad Ariani H, Zhang X, Chung S, Deng N et al. Disabling the nuclear translocalization of RelA/NF-κB by a small molecule inhibits triple-negative breast cancer growth. Breast Cancer: Targets and Therapy. 2021 Jul: 419-30. doi: 10.2147/BCTT.S310231.

Palayoor ST, Bump EA, Calderwood SK, Bartol S, Coleman CN. Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma cells. Clinical cancer research: an Official Journal of the American Association for Cancer Research. 1998 Mar; 4(3): 763-71.

Takada Y, Bhardwaj A, Potdar P, Aggarwal BB. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-κB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004 Dec; 23(57): 9247-58. doi: 10.1038/sj.onc.1208169.

Ashaq A, Maqbool MF, Maryam A, Khan M, Shakir HA, Irfan M et al. Hispidulin: A novel natural compound with therapeutic potential against human cancers. Phytotherapy Research. 2021 Feb; 35(2): 771-89. doi: 10.1002/ptr.6862.

Trott O and Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry. 2010 Jan; 31(2): 455-61. doi: 10.1002/jcc.21334.

Chen FE, Huang DB, Chen YQ, Ghosh G. Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA. Nature. 1998 Jan; 391(6665): 410-3. doi: 10.1038/34956.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H et al. The protein data bank. Nucleic acids research. 2000 Jan; 28(1): 235-42. doi: 10.1093/nar/28.1.235.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S et al. PubChem 2019 update: improved access to chemical data. Nucleic acids research. 2019 Jan; 47(D1): D1102-9. doi: 10.1093/nar/gky1033

Morris GM, Huey R, Olson AJ. Using autodock for ligand‐receptor docking. Current protocols in bioinformatics. 2008 Dec; 24(1): 8-14. doi: 10.1002/0471250953.bi0814s24.

Salaria P, Akshinthala P, Kapavarapu R. Identification of novel C-15 fluoro isosteviol derivatives for GABA-AT inhibition by in silico investigations. Journal of Molecular Modeling. 2023 Mar; 29(3): 76. doi: 10.1007/s00894-023-05479-7.

Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific reports. 2017 Mar; 7(1): 42717. doi: 10.1038/srep42717.

Curreli F, Kwon YD, Belov DS, Ramesh RR, Kurkin AV, Altieri A et al. Synthesis, antiviral potency, in vitro ADMET, and X-ray structure of potent CD4 mimics as entry inhibitors that target the Phe43 cavity of HIV-1 gp120. Journal of medicinal chemistry. 2017 Apr; 60(7): 3124-53. doi: 10.1021/acs.jmedchem.7b00179.

Savitri D, Wahyuni S, Bukhari A, Djawad K, Hatta M. Molecular docking of active compounds from Kepok banana (Musa acuminata x balbisiana) peels extract on the NF- pathway in acne vulgaris. NVEO-Natural Volatiles & Essential Oils Journal| NVEO. 2021 Nov: 2240-8.

Kadioglu O, Nass J, Saeed ME, Schuler B, Efferth T. Kaempferol is an anti-inflammatory compound with activity towards NF-κB pathway proteins. Anticancer research. 2015 May; 35(5): 2645-50.

Vanajothi R and Srinivasan P. An anthraquinone derivative from Luffa acutangula induces apoptosis in human lung cancer cell line NCI-H460 through p53-dependent pathway. Journal of Receptors and Signal Transduction. 2016 May; 36(3): 292-302. doi: 10.3109/10799893.2015.1108335.

Shrivastava S, Kulkarni P, Thummuri D, Jeengar MK, Naidu VG, Alvala M et al. Piperlongumine, an alkaloid causes inhibition of PI3 K/Akt/mTOR signaling axis to induce caspase-dependent apoptosis in human triple-negative breast cancer cells. Apoptosis. 2014 Jul; 19: 1148-64. doi: 10.1007/s10495-014-0991-2.

Purawarga Matada GS, Dhiwar PS, Abbas N, Singh E, Ghara A, Das A et al. Molecular docking and molecular dynamic studies: screening of phytochemicals against EGFR, HER2, estrogen and NF-KB receptors for their potential use in breast cancer. Journal of Biomolecular Structure and Dynamics. 2022 Jul; 40(13): 6183-92. doi: 10.1080/07391102.2021.1877823.

Ranganatha S, Shruthi SD, Govindappa M, Ramachandra YL. In silico studies of NF-κB protein as anti-cancer and anti-inflammatory target. Journal of Computational Methods in Molecular Design. 2013 Dec; 3: 26-33.

Ren J, Su D, Li L, Cai H, Zhang M, Zhai J et al. Anti-inflammatory effects of Aureusidin in LPS-stimulated RAW264. 7 macrophages via suppressing NF-κB and activating ROS-and MAPKs-dependent Nrf2/HO-1 signaling pathways. Toxicology and Applied Pharmacology. 2020 Jan; 387: 114846. doi: 10.1016/j.taap.2019.114846.

Tiwari P, Mishra BN, Sangwan NS. Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. Biomed Research International. 2014 Jan; 2014. doi: 10.1155/2014/830285.

Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug discovery today: Technologies. 2004 Dec; 1(4): 337-41. doi: 10.1016/j.ddtec.2004.11.007.



DOI: 10.54393/fbt.v3i03.55
Published: 2023-12-31

How to Cite

Ishaq, M., Mansha, M., Maqbool, M. F., Khan, M., & Saeed, A. (2023). Computational Profile of Novel Natural Bioactive Inhibitors of NF-κB: Computational Profile of Novel Natural Bioactive Inhibitors. Futuristic Biotechnology, 3(03), 51–58.


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