Identification of bioactive inhibitors in dragon fruit (Hylocereus undatus) targeting TOP2A protein in human breast cancer

Authors

• Md Iftehimul
• Soharth Hasnat
• Md Hasibur Rahman
• Md Shohel Hossain
• Md Arju Hossain
• Abdul Barik
• Md Faisal Amin, The University of Texas Rio Grande Valley
• Dipta Dey
• Tofazzal Islam
• M. Nazmul Hoque

Document Type

Article

Publication Date

4-2026

Abstract

Breast cancer (BC) is the second most common cause of cancer-related mortality worldwide. Topoisomerase II alpha (TOP2A), a key enzyme involved in DNA replication and repair, represents an important biomarker and a promising therapeutic target in BC. This study investigated the therapeutic potential of bioactive compounds from dragon fruit (Hylocereus undatus) as inhibitors of TOP2A using computational biology approaches. A total of 72 phytochemicals were retrieved from the PubChem database and evaluated for binding affinity, toxicity, drug-likeness, and inhibitory potential against TOP2A. Among these, fifteen compounds satisfied Lipinski's rule of five and were predicted to be non-toxic and non-carcinogenic. Further molecular screening identified four compounds, Phlorizin, Beta-Glucogallin, Peoniflorin, and Alpha-Tocopherol as strong TOP2A inhibitors, with binding energies ranging from −7.4 and −9.5 kcal/mol. Thermodynamic analysis showed that all four had favorable Gibbs free energy values, indicating spontaneous binding to TOP2A. Thermodynamic analysis revealed favorable Gibbs free energy values, indicating spontaneous binding to TOP2A. Two hundred nanosecond (200 ns) molecular dynamics simulations were performed to assess the conformational stability and binding interactions of the selected compounds with TOP2A, using doxorubicin as a reference control. Throughout the simulations, all phytochemicals demonstrated stable root mean square deviation values, low fluctuations, consistent radius of gyration, and preserved key intermolecular interactions, including hydrogen bonds and hydrophobic contacts. Pharmacokinetic analysis further indicated favorable drug-like properties, while network pharmacology identified key cancer-related targets, such as TP53 and EGFR, supporting the therapeutic relevance of these compounds in BC. Overall, Phlorizin, Beta-Glucogallin, Peoniflorin, and Alpha-Tocopherol demonstrated strong in silico potential as TOP2A inhibitors, suggesting possible therapeutic applications in BC and other cancers.

Comments

© 2026 The Authors. Published by Elsevier Ltd.

Recommended Citation

Iftehimul, Md, Soharth Hasnat, Md Hasibur Rahman, Md Shohel Hossain, Md Arju Hossain, Abdul Barik, Md Faisal Amin, Dipta Dey, Tofazzal Islam, and M. Nazmul Hoque. "Identification of bioactive inhibitors in dragon fruit (Hylocereus undatus) targeting TOP2A protein in human breast cancer." Heliyon 12, no. 6 (2026). https://doi.org/10.1016/j.heliyon.2026.e44792

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Heliyon

DOI

10.1016/j.heliyon.2026.e44792