In silico molecular docking of chelidonic acid across multiple targets associated with carcinogenesis
DOI:
https://doi.org/10.70066/jahm.v14i9.3041Keywords:
Angiogenesis, Apoptosis, Cancer, Cell proliferation, Chelidonic acid, Molecular docking, Oxidative stress.Abstract
Background: Cancers can result from dysfunction of interrelated molecular pathways, including oxidative stress, inflammation, proliferation, apoptosis, and angiogenesis. Chelidonic acid (CA) is a naturally occurring organic heterocyclic acid with reported antioxidant and anti-inflammatory effects. However, its molecular interactions with cancer-related targets remain unexplored. Objective: This study aims to investigate CA's molecular interaction profile against various proteins associated with carcinogenesis. Methods: We conducted molecular docking studies using AutoDock Vina with 23 cancer-associated protein targets, including proteins involved in oxidative stress and antioxidant defense, inflammatory responses, apoptosis, cell proliferation and cell-cycle regulation, PI3K/AKT/mTOR signaling, invasion, and angiogenesis. The interactions between proteins and ligands were visualized using BIOVIA Discovery Studio Visualizer․ Ligand efficiency (LE) was calculated as docking score/number of heavy atoms in CA․ The docking protocol was further validated by redocking suitable co-crystallized/native ligands using the same docking parameters, and RMSD values were calculated using PyMOL. Results: CA showed predicted docking scores ranging from −7.5 to −5.4 kcal/mol across the 23 target proteins. The most negative predicted docking score was observed for CAT (-7.5), followed by GR (-6.9), caspase-9 (-6.7), COX-2 (-6.6), MMP-9 (-6.6), and PI3Kα (-6.5). Other proteins that were found to have predicted molecular interactions with p53 (-6․4), caspase-3 (-6․3)‚ AKT1 (-6․3)‚ Keap1 (-6․3)‚ MMP-2 (-6․2)‚ HO-1 (-6․1)‚ VEGFR2 (-6․1)‚ GST (-6․0)‚ c-Myc/Max (-5․9)‚ IL-6 (-5․9)‚ mTOR (-5.9), TNF-α (-5․8)‚ NF-κB p52 (-5․6)‚ iNOS (-5․6)‚ GPX4 (-5․5)‚ PCNA (-5․5) and SOD (-5․4)․ The various binding interactions observed with protein targets, including hydrogen, carbon-hydrogen, π-mediated interactions, van der Waals forces and hydrophobic contacts. Redocking validation was performed for 10 targets, showing RMSD values below 2.0 Å. Ligand efficiency values ranged from -0.577 to -0.415 kcal/mol/HA, with the more negative LE observed for CAT. Conclusion: These findings indicate that CA can interact with several interconnected molecular pathways involved in carcinogenesis.
References
Nosrati N, Bakovic M, Paliyath G. Molecular mechanisms and pathways as targets for cancer prevention and progression with dietary compounds. Int. J. Mol. Sci. 2017;18(10):2050. Available from: [https://doi.org/10.3390/ijms18102050](https://doi.org/10.3390/ijms18102050) [cited 2026 Oct 1]
Zhang KY, Zhu XZ, Yan YX, Ying XH, Zhang J, Wang ZH. Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets. Signal Transduct. Target. Ther. 2026;11(1):280. Available from: [https://doi.org/10.1038/s41392-026-02850-x](https://doi.org/10.1038/s41392-026-02850-x) [cited 2026 Oct 1]
Hayes JD, Dinkova-Kostova AT, Tew KD. Oxidative stress in cancer. Cancer cell. 2020;38(2):167-197. Available from: [https://doi.org/10.1016/j.ccell.2020.06.001](https://doi.org/10.1016/j.ccell.2020.06.001) [cited 2026 Oct 1]
Liang X, Weng J, You Z, Wang Y, Wen J, Xia Z, Huang S, Luo P, Cheng Q. Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers. Mol. Cancer. 2025;24(1):219. Available from: [https://doi.org/10.1186/s12943-025-02375-x](https://doi.org/10.1186/s12943-025-02375-x) [cited 2026 Oct 1]
Southey MW, Brunavs M. Introduction to small molecule drug discovery and preclinical development. Front. Drug Discov. 2023;3:1314077. Available from: [https://doi.org/10.3389/fddsv.2023.1314077](https://doi.org/10.3389/fddsv.2023.1314077) [cited 2026 Oct 1]
Poh-Yen K. Phytochemical small molecules as potential anti-angiogenesis targeted therapy for triple-negative breast cancer. Rev. Bras. Farmacogn. 2024;34(3):451-466. Available from: [https://doi.org/10.1007/s43450-023-00491-7](https://doi.org/10.1007/s43450-023-00491-7) [cited 2026 Oct 1]
Qian R, Ge J, Fan N, Sun Z, Zhao C, Sun Y, Li Y, Li Y, Fu H. Natural products in cancer prevention and therapy: current challenges and future directions. MedComm. 2026;7(2):e70585. Available from: [https://doi.org/10.1002/mco2.70585](https://doi.org/10.1002/mco2.70585) [cited 2026 Oct 1]
Romanu R, Liga S, Tripon MR, Huiban F, Iliescu D, Dehelean CA, Camelia T. Chelidonium majus L.: A current perspective on isoquinoline alkaloids, emerging phytochemicals, alkaloid biosynthesis, and biological activities. Plants. 2025;14(17):2627. Available from: [https://doi.org/10.3390/plants14172627](https://doi.org/10.3390/plants14172627) [cited 2026 Oct 1]
Harish K, Sivasankaran SM, Manoharan S, Sakthisankaran SM. A brief review on pharmacological efficacy of chelidonic acid. Journal of Drug Delivery & Therapeutics (JDDT). 2025;15(9):115. Available from: [https://doi.org/10.22270/jddt.v15i9.7352](https://doi.org/10.22270/jddt.v15i9.7352) [cited 2026 Oct 1]
Ru X, Xu L, Han W, Zou Q. In silico methods for drug-target interaction prediction. Cell Rep. Methods. 2025;5(10). Available from: [https://doi.org/10.1016/j.crmeth.2025.101184](https://doi.org/10.1016/j.crmeth.2025.101184) [cited 2026 Oct 1]
Khairnar SI, Kulkarni YA, Murugesan S, Singh K. Effects of acute and repeated dose toxicity profiling of chelidonic acid in rats: in silico and in vivo evidence. Chem. Biodivers. 2023;20(12):e202301241. Available from: [https://doi.org/10.1002/cbdv.202301241](https://doi.org/10.1002/cbdv.202301241) [cited 2026 Oct 1]
Schultes S, de Graaf C, Haaksma EE, de Esch IJ, Leurs R, Krämer O. Ligand efficiency as a guide in fragment hit selection and optimization. Drug Discov. Today Technol. 2010;7(3):e157-62. Available from: [https://doi.org/10.1016/j.ddtec.2010.11.003](https://doi.org/10.1016/j.ddtec.2010.11.003) [cited 2026 Oct 1]
Choudhari SK, Chaudhary M, Gadbail AR, Sharma A, Tekade S. Oxidative and antioxidative mechanisms in oral cancer and precancer: a review. Oral Oncol. 2014;50(1):10-18. Available from: [https://doi.org/10.1016/j.oraloncology.2013.09.011](https://doi.org/10.1016/j.oraloncology.2013.09.011) [cited 2026 Oct 1]
He L, He T, Farrar S, Ji L, Liu T, Ma X. Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell. Physiol. Biochem. 2017;44(2):532-553. Available from: [https://doi.org/10.1159/000485089](https://doi.org/10.1159/000485089) [cited 2026 Oct 1]
Marinescu R, Marinescu D, Preda D, Ciurea AM, Popa P, Boldeanu L, et al . Oxidative stress and inflammation in colorectal cancer–redox–immune crosstalk, biomarkers, and translational implications: A qualitative systematic review. Life (Basel). 2026;16(3):424. Available from: [https://doi.org/10.3390/life16030424](https://doi.org/10.3390/life16030424) [cited 2026 Oct 1]
Pellarin I, Dall’Acqua A, Favero A, Segatto I, Rossi V, Crestan N, et al . Cyclin-dependent protein kinases and cell cycle regulation in biology and disease. Signal Transduct. Target. Ther. 2025;10(1):11. Available from: [https://doi.org/10.1038/s41392-024-02080-z](https://doi.org/10.1038/s41392-024-02080-z) [cited 2026 Oct 1]
Abuetabh Y, Wu HH, Chai C, Al Yousef H, Persad S, Sergi CM, et al . DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities. Exp. Mol. Med. 2022;54(10):1658-1669. Available from: [https://doi.org/10.1038/s12276-022-00863-4](https://doi.org/10.1038/s12276-022-00863-4) [cited 2026 Oct 1]
Morgos DT, Stefani C, Miricescu D, Greabu M, Stanciu S, Nica S, et al . Targeting PI3K/AKT/mTOR and MAPK signaling pathways in gastric cancer. Int. J. Mol. Sci. 2024;25(3):1848. Available from: [https://doi.org/10.3390/ijms25031848](https://doi.org/10.3390/ijms25031848) [cited 2026 Oct 1]
Tan Y, Wang Z, Xu M, Li B, Huang Z, Qin S, et al . Oral squamous cell carcinomas: state of the field and emerging directions. Int. J. Oral Sci. 2023;15(1):44. Available from: [https://doi.org/10.1038/s41368-023-00249-w](https://doi.org/10.1038/s41368-023-00249-w) [cited 2026 Oct 1]
Kato K, Hara A, Kuno T, Kitaori N, Huilan Z, Mori H, et al . Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas: manifestation and localization of their activity. J. Cancer Res. Clin. Oncol. 2005;131(6):340-346. Available from: [https://doi.org/10.1007/s00432-004-0654-8](https://doi.org/10.1007/s00432-004-0654-8) [cited 2026 Oct 1]
Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, et al . The roles of matrix metalloproteinases and their inhibitors in human diseases. Int. J. Mol. Sci. 2020;21(24):9739. Available from: [https://doi.org/10.3390/ijms21249739](https://doi.org/10.3390/ijms21249739) [cited 2026 Oct 1]
Shaw P, Dwivedi SK, Bhattacharya R, Mukherjee P, Rao G. VEGF signaling: role in angiogenesis and beyond. Biochim. Biophys. Acta - Rev. Cancer. 2024;1879(2):189079. Available from: [https://doi.org/10.1016/j.bbcan.2024.189079](https://doi.org/10.1016/j.bbcan.2024.189079) [cited 2026 Oct 1]
Monaci S, Coppola F, Filippi I, Falsini A, Carraro F, Naldini A. Targeting hypoxia signaling pathways in angiogenesis. Front. Physiol. 2024;15:1408750. Available from: [https://doi.org/10.3389/fphys.2024.1408750](https://doi.org/10.3389/fphys.2024.1408750) [cited 2026 Oct 1]
Khairnar SI, Kulkarni YA, Singh K. Mitigation of cisplatin-induced nephrotoxicity by chelidonic acid in Wistar rats. J. Trace Elem. Med. Biol. 2024;81:127321. Available from: [https://doi.org/10.1016/j.jtemb.2023.127321](https://doi.org/10.1016/j.jtemb.2023.127321) [cited 2026 Oct 1]
Khairnar SI, Kulkarni YA, Singh K. Cardioprotective effect of chelidonic acid against doxorubicin-induced cardiac toxicity in rats. Rev. Port. Cardiol. 2025;44(3):141-153. Available from: [https://doi.org/10.1016/j.repc.2024.06.003](https://doi.org/10.1016/j.repc.2024.06.003) [cited 2026 Oct 1]
Khairnar SI, Kulkarni YA, Singh K. Neuroprotective effect of chelidonic acid through oxidative stress reduction in paclitaxel-induced peripheral neuropathy in rats. Naunyn Schmiedebergs Arch Pharmacol. 2025;398(4):4435-4447. Available from: [https://doi.org/10.1007/s00210-024-03550-5](https://doi.org/10.1007/s00210-024-03550-5) [cited 2026 Oct 1]
Kim SJ, Kim DS, Lee SH, Ahn EM, Kee JY, Hong SH. Chelidonic acid ameliorates atopic dermatitis symptoms through suppression the inflammatory mediators in in vivo and in vitro. Appl. Biol. Chem. 2023;66(1):12. Available from: [https://doi.org/10.1186/s13765-022-00763-1](https://doi.org/10.1186/s13765-022-00763-1) [cited 2026 Oct 1]
Turkoglu B, Mansuroglu B. Investigating the effects of chelidonic acid on oxidative stress-induced premature cellular senescence in human skin fibroblast cells. Life (Basel). 2024;14(9):1070. Available from: [https://doi.org/10.3390/life14091070](https://doi.org/10.3390/life14091070) [cited 2026 Oct 1]
Shin HJ, Kim HL, Kim SJ, Chung WS, Kim SS, Um JY. Inhibitory effects of chelidonic acid on IL-6 production by blocking NF-κB and caspase-1 in HMC-1 cells. Immunopharmacol. Immunotoxicol. 2011;33(4):614-619. Available from: [https://doi.org/10.3109/08923973.2011.552508](https://doi.org/10.3109/08923973.2011.552508) [cited 2026 Oct 1]
Kenny PW. The nature of ligand efficiency. J. Cheminform. 2019;11(1):8. Available from: [https://doi.org/10.1186/s13321-019-0330-2](https://doi.org/10.1186/s13321-019-0330-2) [cited 2026 Oct 1]
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