Exploring lichen-derived compounds as potential anti-cervical cancer agents: an DFT and MD simulation analysis

Lichen-derived compounds have demonstrated promising anti-cancer potential, attributed to their bioavailability and unique structural properties. This study evaluates the therapeutic efficacy of five lichen compounds-fumarprotocetraric acid, salazinic acid, evernic acid, sekikaic acid, and lobaric acid-against cervical cancer, using molecular docking, density functional theory (DFT), and molecular dynamics (MD) simulations. Drug-likeness validation confirmed that evernic acid, topotecan, and ifosfamide adhere to Lipinski's rule of five. Molecular docking against ten cervical cancer target proteins revealed high binding affinities, with fumarprotocetraric acid (- 10.4 kcal/mol against 1KTZ), salazinic acid (- 10.9 kcal/mol against 2PVF), and evernic acid (- 11.3 kcal/mol against 2BIM) outperforming standard drugs such as topotecan (- 10.2 kcal/mol against 2BIM). ADME (Absorption, Distribution, Metabolism, and Excretion) profiling confirmed favorable pharmacokinetics, with salazinic acid exhibiting the highest human intestinal absorption (89.35%). Bioactivity analysis further supported enhanced activity for lichen compounds (0.0-5.0) compared to standard drugs (- 5.0-0.0). DFT analysis demonstrated lower energy gaps for fumarprotocetraric acid (- 0.1806 eV) and salazinic acid (- 0.1632 eV), indicating high chemical reactivity. MD simulations confirmed greater stability of lichen-protein complexes over anti-cancer drugs, with the 2BIM-evernic acid complex displaying the highest Molecular Mechanics Generalized Born Surface Area (MMGBSA) binding energy (- 114.29 kcal/mol). These findings highlight the therapeutic potential of fumarprotocetraric acid, salazinic acid, and evernic acid, warranting further preclinical investigations to establish their efficacy against cervical cancer.