Terminalia bentzoe (T. bentzoe) is widely recognized in ethnomedicine for its use in treating a range of health conditions, including gastrointestinal disorders, menstrual pain, febrile illnesses, and respiratory symptoms associated with the common cold. The present investigation aimed to characterize the phytochemical constituents of this plant, evaluate its in vitro cytotoxic activity against breast cancer cells, and support the experimental findings through comprehensive computational analyses, including molecular docking, ADMET prediction, and molecular dynamics simulations. Chemical investigation of the n-hexane extract of T. bentzoe led to the isolation of six triterpenoid compounds (1–6), which were structurally elucidated using spectroscopic techniques. The identified metabolites were α-amyrin (1), β-amyrin (2), lupeol (3), oleanolic acid (4), ursolic acid (5), and betulin (6). These compounds were screened for antiproliferative activity against the MCF-7 human breast cancer cell line. Oleanolic acid (4) and ursolic acid (5) exhibited superior cytotoxic potency, as indicated by their IC₅₀ values, whereas β-amyrin (2) and betulin (6) demonstrated minimal growth-inhibitory effects. Computational docking studies revealed that compounds 1, 3, 4, and 5 interact favorably with several critical cancer-associated molecular targets, including epidermal growth factor receptor (EGFR), estrogen receptor (ER), and cyclin-dependent kinase 2 (CDK2). Pharmacokinetic and toxicity predictions showed that all isolated compounds adhered to Lipinski’s rule of five, reflecting acceptable drug-likeness profiles. Among the tested metabolites, oleanolic acid (4) displayed the most advantageous in silico characteristics, including high predicted oral absorption, desirable pharmacokinetic properties, and low toxicity risk. The stability of oleanolic acid (4) within the binding pockets of EGFR, ER, and CDK2 was further validated through molecular dynamics simulations. The analyzed parameters, including RMSD (0.20–0.45 nm), RMSF (0.10–0.40 nm), solvent-accessible surface area (120–150 nm2), and radius of gyration (1.80–2.10 nm), remained within stable ranges throughout the simulation period. Taken together, these findings identify oleanolic acid (4) as a compelling candidate for further preclinical evaluation as an anticancer agent. Moreover, the concordance between computational and experimental results enabled the ranking of anticancer efficacy as 4 > 5 > 1 > 6 > 2. Overall, the triterpenes obtained from T. bentzoe exhibit noteworthy therapeutic potential and justify continued investigation for diverse biomedical applications.

Multitarget anticancer potential of Terminalia bentzoe triterpenes: in vitro cytotoxicity and computational validation

期刊论文
发表日期：

2026年5月12日

查看全文

Doaa A. Abdelrheem,
Osama M. Ahmed,
Ahmed F. El-Sayed,
Ashraf M. Mohamed,
Sayed A. Ahmed

摘要

Terminalia bentzoe (T. bentzoe) is widely recognized in ethnomedicine for its use in treating a range of health conditions, including gastrointestinal disorders, menstrual pain, febrile illnesses, and respiratory symptoms associated with the common cold. The present investigation aimed to characterize the phytochemical constituents of this plant, evaluate its in vitro cytotoxic activity against breast cancer cells, and support the experimental findings through comprehensive computational analyses, including molecular docking, ADMET prediction, and molecular dynamics simulations. Chemical investigation of the n-hexane extract of T. bentzoe led to the isolation of six triterpenoid compounds (1–6), which were structurally elucidated using spectroscopic techniques. The identified metabolites were α-amyrin (1), β-amyrin (2), lupeol (3), oleanolic acid (4), ursolic acid (5), and betulin (6). These compounds were screened for antiproliferative activity against the MCF-7 human breast cancer cell line. Oleanolic acid (4) and ursolic acid (5) exhibited superior cytotoxic potency, as indicated by their IC₅₀ values, whereas β-amyrin (2) and betulin (6) demonstrated minimal growth-inhibitory effects. Computational docking studies revealed that compounds 1, 3, 4, and 5 interact favorably with several critical cancer-associated molecular targets, including epidermal growth factor receptor (EGFR), estrogen receptor (ER), and cyclin-dependent kinase 2 (CDK2). Pharmacokinetic and toxicity predictions showed that all isolated compounds adhered to Lipinski’s rule of five, reflecting acceptable drug-likeness profiles. Among the tested metabolites, oleanolic acid (4) displayed the most advantageous in silico characteristics, including high predicted oral absorption, desirable pharmacokinetic properties, and low toxicity risk. The stability of oleanolic acid (4) within the binding pockets of EGFR, ER, and CDK2 was further validated through molecular dynamics simulations. The analyzed parameters, including RMSD (0.20–0.45 nm), RMSF (0.10–0.40 nm), solvent-accessible surface area (120–150 nm²), and radius of gyration (1.80–2.10 nm), remained within stable ranges throughout the simulation period. Taken together, these findings identify oleanolic acid (4) as a compelling candidate for further preclinical evaluation as an anticancer agent. Moreover, the concordance between computational and experimental results enabled the ranking of anticancer efficacy as 4 > 5 > 1 > 6 > 2. Overall, the triterpenes obtained from T. bentzoe exhibit noteworthy therapeutic potential and justify continued investigation for diverse biomedical applications.