Polyphenols from Prunus armeniaca.L as Promising Anticancer (Cervical Cancer): In silico studies and in vivo safety assessment

Some anogenital tract malignancies have high-risk human papillomavirus (HPV) infections as their etiological cause. Although many HPV preventative vaccines have been licensed, there is still a need for medication that targets the infection and its carcinogenic effects. One of the important elements in cell immortalization and tumor development in HPV-positive cells has been identified as the viral oncoprotein E6. The cellular ubiquitin ligase E6AP interacts with E6, which can facilitate the degradation of the tumor suppressor protein p53. One of the best ways to prevent the maintenance and growth of infected cells is to block the creation of the E6-E6AP complex. The present study aims to determine the ability of polyphenols identified in Prunus armeniaca.L, to target the HPV16 virus by virtual high-throughput screening and molecular docking, and to evaluate the safety of this plant in vivo. In silico, the PDB: 4GIZ structure of E6HPV16 was prepared as a target by Discovery Studio 2021. Virtual screening of 47 polyphenols was performed by the iGEMDOCK program, followed by an evaluation of potential inhibitors based on docking affinities obtained from the The SYBYL-X Surflex-Dock module v2.0, 21. In vivo toxicity studies of Prunus armeniaca. L aqueous extract was also conducted in Wistar rats. Of all the polyphenols investigated in this study, the compounds 3-pCoumaroylquinic, 5-pCoumaroyloquinic, Epicatechin, and Dimethoxyflavone were predicted to have the highest binding affinity for E6HPV16, also revealed several interactions with the E6 binding site area. A study on acute in vivo toxicity of Prunus armeniaca .L aqueous extract was conducted and didn't produce any harmful effects. Moreover, Epicatechin, a dimethoxyflavone from Prunus armeniaca.L, 3-pCoumaroylquinic, 5-pCoumaroylquinic, and 5-pCoumaroyloquinic were chosen as possible E6HPV16 inhibitors for novel medication development.