Secondary Metabolite Profiling, Antiproliferative Evaluation, and Terpenoid Prioritization of Indonesian Cardamom (Amomum compactum) Accessions

This study compared secondary-metabolite profiles, IC50-based antiproliferative activity, and relative selectivity of four Indonesian cardamom (Amomum compactum Soland. ex Maton) accessions: Bogor white, Bogor red, Sukabumi, and Ciamis. Ethanol and ethyl acetate extracts were evaluated in MCF-7, MCM-B2, and MCA-B1 tumor-derived cells, with Vero cells as a non-tumor-derived reference and profiled by untargeted LC-MS/MS. Putatively annotated metabolites were further assessed using chemometrics, terpenoid-focused network pharmacology, molecular docking, and 50 ns molecular dynamics simulation. Extract IC50 values ranged from 0.959 to 2.210 mg mL−1 in MCF-7, 0.818 to 2.733 mg mL−1 in MCM-B2, and 1.382 to 3.426 mg mL−1 in MCA-B1 cells, while Vero values ranged from 2.762 to 4.000 mg mL−1. MCF-7 cells generally showed the greatest overall sensitivity, although the lowest individual IC50 occurred with Sukabumi ethyl acetate extract in MCM-B2 cells. Ciamis ethyl acetate extract showed higher relative selectivity toward MCF-7 and MCM-B2 cells. LC-MS/MS putatively annotated 36 metabolites, with terpenoid-related compounds predominating. Kaur-16-ene was computationally prioritized based on predicted interactions with ESR1, EGFR, SCN5A, and CCND1 and short-timescale ESR1-complex stability. These findings demonstrate accession- and solvent-associated differences and support kaur-16-ene for further experimental validation.