Exploring the therapeutic potential of Esculin in the treatment of bladder cancer

Abstract

This research highlights the potential of Esculin as a promising treatment for bladder cancer, supported by insilico molecular docking and network pharmacology analyses. The study identified key targets, including GAPDH, TNF, MMP9, EGFR, and IL2, which play crucial roles in pathways associated with bladder cancer, such as IL-17 and TNF signalling. Esculin showed a strong binding affinity to these targets, especially to TNF, indicating its therapeutic potential. Calculations of binding free energy using the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method revealed the interaction dynamics, with the TNF-Esculin complex having a favourable binding free energy of -8.92 kcal/mol. This was primarily influenced by van der Waals forces (-16.1 kcal/mol) and electrostatic interactions (-3.57 kcal/mol), along with significant solvation effects. Energy decomposition analysis identified specific residues in the binding pocket that contribute to the stability of the complex, reinforcing Esculin's prospects for drug development. Moreover, principal component analysis (PCA) of the molecular dynamics (MD) simulations illustrated the dynamic behaviour of the TNF-Esculin complex, indicating a high level of stability, as evidenced by its smaller spatial occupation in trajectory plots. Overall, these findings strongly advocate for further exploration of Esculin as a novel therapeutic agent for bladder cancer, highlighting the need for additional experimental validation and drug development initiatives.