Integrative network pharmacology and genomic analysis of esculin targeting PARP1 in cervical cancer: Insights from ADME profiling, molecular docking, and biomarker discovery

Abstract

Cervical cancer remains a serious global health issue, particularly in low- and middle-income countries, with inadequate access to early detection and diagnostics. This study investigates the anticancer effect of esculin, a coumarin known for its pharmacological benefits, as a safer and more effective alternative to standard chemotherapeutics. This research implements an integrative in silico method, which includes ADME profiling, toxicity prediction, molecular docking, molecular dynamics (MD) simulations, and network pharmacology analyses. Esculin performed well in drug-likeness properties and showed satisfactory water solubility and low predicted toxicity, which is even better than that of the reference drug paclitaxel in safety and pharmacokinetics. Although no direct connection was established between esculin's predicted targets and genes perturbed in cervical cancer, PARP1 came up as a candidate target that is functionally and biologically relevant, since the protein is involved in DNA repair and is overexpressed in cervical tumours. Molecular docking revealed that esculin binds strongly to PARP1and interacts with ASP770 and ARG878. A subsequent 100 ns molecular dynamics (MD) simulation experiment showed the constant RMSD and hydrogen bonding profiles that were consistent and thus proved the stability of the complex structure. Protein-protein interaction and enrichment analyses supported PARP1's role in critical cancer-associated pathways, particularly in DNA damage response and chromatin remodelling. Considering all the findings, the efforts to develop a targeted cervical cancer therapy with esculin as a potential candidate are gaining traction and being warranted by further experimental validation.