VOLUME 18 (Supplement)

In silico screening suggests dicumarol and demethylwedelolactone as E6-p53 inhibitors in the context of cervical cancer treatment

HPV E6 oncoprotein, together with E6AP can degrade p53, causing genomic instability. This leads to cervical cancer (most prevalent cancer among women worldwide). Many non-flavonoid polyphenols have anti-cancer properties but, despite being a wide family of compounds, remain unexplored as E6-E6AP-p53 binding site inhibitors. We analysed non-flavonoid polyphenols (ZINC15 databank, 285 compounds) and their binding to the site using in silico techniques to nominate potential drug candidates. We screened them using Lipinski's rule of five. AutoDock Vina Molecular docking against the binding site suggested dicumarol and demethylwedelolactone (DWL) as potential E6 inhibitors, which have not yet been studied for this purpose, with higher affinity than daphnoretin, a non-flavonoid polyphenol with known inhibitory properties against E6. Target Prediction by ChEMBL revealed that both compounds potentially interact with the cancer-marking genes ROS1 and NQO1. ADMET profile suggests both compounds may be developed into an oral drug.