Abstract
Ovarian cancer being the deadliest malignancy for women, with conventional medication often limited by side effects on normal cell. Phytocompounds based therapies have promising alternative due to their fewer adverse side effects and diverse therapeutic benefits. Lichen shows relationship between algae and fungi, are known for producing unique secondary metabolites with potent bioactivity. In this study, Usnea longissima was investigated for its anticancer properties against ovarian cancer using in-silico approaches such as ADMET screening, molecular docking, molecular dynamics simulation, and network pharmacology. Bioactive compounds were first identified by GC-MS analysis. Phytocompounds were screened out by ADME analysis. Two particular compounds 7-acetyl-1,1,3,4,4,6-hexamethyl tetralin and 1,2-benzenedicarboxylic acid were focused based on their strong their binding affinities. These compounds exhibit significant binding affinities to ovarian cancer proteins such as FGFR3 and AKT1, MSH6 and ESR1 with docking scores of - 9.5, - 9.5, - 8.2, - 8.0 kcal/mol respectively, comparable to the binding affinity of the reference drug Pemigatinib. Simulations yielded extremely satisfactory findings for the protein ligand RMSD and RMSF, Rg, SASA, PSA, MM-GBSA profile and network analysis revealed a strong degree of inter-protein association. Despite the work on lichens, only a limited number of lichen species have been explored for their biological efficacy and their therapeutic potential as medicine. In this study, we highlighted the potential of lichen-derived phytocompounds in ovarian cancer treatment and highlights specially 7-acetyl-1, 1, 3, 4, 4, 6-hexamethyl tetralin as promising candidates for future drug development. Further exploration of lichen metabolites may offer novel, effective, and safer therapeutic strategies against ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00408-3.