Introduction: Marchantia paleacea contains macrocyclic bisbibenzyls, including marchantins with known cytotoxic, antioxidant, and antimicrobial activities, with no known mechanism of action. This study aimed to evaluate the cytotoxic potential of three solvent extracts—70% ethanol (EEMP), ethyl acetate (EAEMP), and n-hexane (NHEMP)—of M. paleacea and to assess molecular interactions of their bioactive compounds through in silico simulations against cancer-related proteins. Methods: Cytotoxicity was determined on MCF-7 and T47D breast cancer cell lines using the MTT assay, with doxorubicin as a positive control. Chemical profiling of the most active extract was performed using Fourier-transform infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS), followed by molecular docking against carbonic anhydrase II (CA-II, PDB ID: 1T47) and cyclin-dependent kinase 2 (CDK2, PDB ID: 1T46). Results: Among the tested extracts, EAEMP showed the strongest cytotoxicity (IC₅₀ = 8.68 µg/mL for MCF-7; 12.78 µg/mL for T47D), compared with EEMP (119.2 and 64.33 µg/mL) and NHEMP (62.07 and 229.8 µg/mL). GC–MS identified Marchantin A, B, and C as major constituents, with Marchantin C exhibiting the highest docking affinity (ΔG = −8.62 kcal/mol) at residues D810 and E640. Conclusion: The ethyl-acetate extract of M. paleacea demonstrates significant in vitro and in silico anticancer potential, suggesting its promise as a semi-polar source of cytotoxic bisbibenzyl compounds for future natural anticancer drug development.
Purkon et al. (2026) studied this question.