COMPUTATIONAL TARGET-BASED SCREENING OF VINCA MINOR PHYTOCHEMICALS FOR URINARY BLADDER CARCINOMA USING NETWORK PHARMACOLOGY AND MOLECULAR DOCKING

Abstract

Background: Urinary bladder carcinoma (UBC) is a common and recurrence-prone malignancy for which current therapeutic options remain constrained by resistance and toxicity. Vinca minor (lesser periwinkle) is a rich source of monoterpenoid indole alkaloids structurally related to clinically established Vinca alkaloid chemotherapeutics, yet its multi-target anticancer potential against UBC has not previously been characterised. Methods: Protein targets of five V. minor phytochemicals (Vincamine, Apovincamine, Vinburnine, Vincadifformine and Vincarubine) were predicted using SwissTargetPrediction and intersected with UBC-associated genes retrieved from GeneCards. The overlapping targets were mapped onto a STRING protein-protein interaction network, analysed in Cytoscape using the CytoHubba MCC algorithm to identify hub genes, and subjected to Gene Ontology and KEGG pathway enrichment via ShinyGO. The leading hub gene was validated by molecular docking with its corresponding phytochemical using AutoDock 4.2.6. Results: Of 271 predicted phytochemical targets, 110 overlapped with 2,534 UBC-associated genes. The resulting network comprised 110 nodes and 961 edges (average degree 17.5; enrichment p < 1.0 × 10⁻¹⁶). MTOR, HIF1A, CASP3, MDM2, ERBB2, MMP9, IGF1R, AKT1, SRC and MMP2 emerged as the top-ranked hub genes. KEGG analysis showed significant enrichment of the Bladder cancer pathway among other cancer-related pathways. Docking of Vincarubine against MTOR (PDB: 8ERA) yielded a binding affinity of −9.4 kcal/mol and ligand efficiency of −0.32 kcal/mol, stabilised by two hydrogen bonds, three carbon-hydrogen bonds and one hydrophobic contact. Conclusion: This integrated in silico analysis identifies a biologically coherent, MTOR-centred multi-target mechanism underlying the potential activity of V. minor against urinary bladder carcinoma and nominates Vincarubine as a mechanistically grounded candidate for further experimental validation.