INTERNATIONAL CONGRESS OF
PharmacoGenetics
In Silico Investigation of Ellagic Acid as a Potential HDAC1 Inhibitor in Breast Cancer
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Elena Ebrahimian,1,* Artemis Azad Ara,2 Masoud Homayouni Tabrizi ,3
1. Department of Biology, Faculty of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
2. Department of Biology, Faculty of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
3. Department of Biology, Ma.C., Islamic Azad University, Mashhad, Iran
- Introduction: Because of its anticancer and antioxidant qualities, ellagic acid, a naturally occurring polyphenolic molecule, has attracted a lot of attention. An essential epigenetic regulator, histone deacetylase 1 (HDAC1), is often overexpressed in breast cancer and is associated with metastasis, tumor growth, and a poor prognosis. This work investigated ellagic acid's potential therapeutic function in the treatment of breast cancer by computationally assessing its inhibitory capacity against HDAC1 using molecular docking.
- Methods: To conduct this study, the structure of the HDAC1 protein was downloaded from the RCSB Protein Data Bank (PDB) with the ID 4BKX and prepared using PyMOL. The ellagic acid was also downloaded from PubChem (CID: 5281855 ) as a ligand. Both were prepared in AutoDockTools. Both the ligand and receptor were converted from PDB to PDBQT format and saved. Docking was performed using AutoDockVina. Ultimately, the best conformation was selected based on the lowest binding energy, and its complex with the receptor was analyzed through the PLIP website to determine the binding site based on the type and residue numbers of the interactions and the binding strength based on the type and number of interactions. These results were also visualized in PyMOL.
- Results: According to the docking results, the lowest binding energy is -7.6 kcal/mol, which is a favorable feature for binding. PLIP analysis showed two hydrophobic interactions between ellagic acid and the residues TYR15 and ILE249 of the receptor. And four hydrogen bonds which three of them were between ellagic acid and ARG36 and one of them was between ellagic acid and HIS39. And salt bridge These interactions are likely to contribute substantially to stabilizing the ellagic acid–HDAC1 complex.
- Conclusion: When considered collectively, the low binding energy, positive docking metrics, and several potent stabilizing interactions between ellagic acid and HDAC1 suggest that ellagic acid may be a candidate HDAC1 inhibitor for further investigation in breast cancer therapy. However, these computational conclusions are preliminary and need to be supported by thorough in vitro biochemical testing and in vivo investigations to determine inhibitory potency and therapeutic potential.
- Keywords: HDAC1, Ellagic Acid, Molecular Docking, Breast Neoplasms.
