New Onoceranoid-Triterpenoids from the Stem Bark of Lansium domesticum Corr. cv. Piedjietan: Structural Characterization and Their Cytotoxic Activity Evaluated by In Vitro and In Silico Approaches

Abstract

This study presents the isolation, characterization and cytotoxic potential of four onoceranoid triterpenoids from the stem bark of Lansium domesticum Corr. cv. Piedjietan, including a newly identified compound, methyl lansic (1), and three known compounds: α,γ-onoceradienedione (2), methyl ester lansiolate (3), and lansiolic acid (4), but reported for the first time in this cultivar. Methyl lansic was tested for cytotoxicity against MCF-7 breast cancer cells. The Results showed that methyl lansic exhibited strong cytotoxic activity with an IC₅₀ value of 7.78 µg/mL, while its IC₅₀ on normal CV-1 cells was substantially higher (620.30 µg/mL), indicating good selectivity toward cancer cells. Molecular docking analysis indicated that methyl lansic and α,γ-onoceradienedione had strong binding affinities to ERα, suggesting their potential as estrogen receptor inhibitors. Molecular dynamics, RMSD/RMSF profiles, persistent key interactions, and favourable MM/GBSA binding energy collectively demonstrate that the methyl lansic–ERα complex is structurally stable and exhibits characteristics consistent with a promising candidate for further evaluation in ERα-positive breast cancer models. These findings expand the phytochemical and pharmacological understanding of Lansium domesticum cv. Piedjietan and highlight its promise as a source of bioactive compounds for the development of anticancer agents.

HIGHLIGHTS

• Methyl lansic was isolated for the first time from Lansium domesticum cv. Piedjietan, expanding the onoceranoid triterpenoid class.
• This study provides the first phytochemical investigation of the Piedjietan cultivar and reports four onoceranoid compounds.
• Methyl lansic demonstrated strong cytotoxicity against MCF-7 cells with an IC₅₀ value of 7.78 µg/mL, indicating its potential as an anticancer agent. The comparison of IC₅₀ values between breast cancer cells MCF-7 and normal CV-1 cells (620.30 µg/mL) shows that methyl lansic is selectively cytotoxic toward breast cancer cells.
• In silico studies including molecular docking, molecular dynamics, and ADMET analyses demonstrated strong binding to ERα and favorable pharmacokinetic properties.
• Bioavailability and safety predictions indicate that methyl lansic is a promising lead compound for the development of therapies targeting estrogen-receptor-positive breast cancer.

GRAPHICAL ABSTRACT