Therapeutic potential of Bergenia ciliata against lung cancer: an integrative molecular docking, ADMET, and molecular...

Bergenia ciliata a himalayan medicinal herb, which has been traditionally used due to its extensive pharmacological properties. Nevertheless, the possible anticancer application on the molecular level has not been fully explored. This experiment was developed to determine the phytochemicals of B. ciliata as natural inhibitors of the epidermal growth factor receptor (EGFR), which is a major target in most epithelial cancers. Phytochemical data on the IMPPAT and PubChem databases were collected. The compounds were using SwissADME and ProTox-II on drug-likeness, absorption, and toxicity. Then six candidates with Lipinski rule and pharmacokinetics conditions were docked to EGFR (PDB ID: 4HJO) with AutoDock vina. The binding affinities of cianidanol and Leucocianidol were the highest, - 8.8 kcal/mol and - 8.7 kcal/mol respectively, as compared to the reference drug erlotinib which has a binding affinity of - 8.3 kcal/Mol. There were several hydrogen bonds and hydrophobic interactions with such critical residues as Lys_721, Thr_766, Asp_831 and Phe_832.Simulations of 100 ns of molecular dynamics showed constant RMSD (0.10-0.20 nm), low fluctuations of residues, and small radius of gyration of all the complexes. MM/PBSA required interactions revealed that the stabilization was dominated by van der Waals forces and electrostatic repulsions with the total binding energies of - 51 kJ/mol, - 46 kJ/mol, and - 34 kJ/mol with cianidanol, leucocianidol, and erlotinib respectively. The studies suggests that EGFR is strongly bound by B. ciliata phytochemicals, and their biocompatible profiles are safer and more inclined to biocompatibility compared to the conventional inhibitor. These findings have indicated that these compounds can be useful lead scaffolds in the development of anticancer drugs in future as they have been shown to possess promising properties that would be further validated by studies conducted in in vitro and in vivo.