Computational and Cytotoxicity Evaluation of Phyllanthus Urinaria-Derived Compounds as Potential Anti-Cervical Cancer Agents via HPV-16 E6 Oncoprotein Inhibition

Cervical cancer remains one of the most lethal cancers affecting women, with infection by high-risk Human Papillomavirus (HR-HPV), especially HPV-16, recognized as a primary cause. Phyllanthus urinaria, a plant that grows in Indonesia, has demonstrated notable both antiviral and anticancer properties. This study aimed to investigate the potential of P. urinaria as both an antiviral and anti-cervical cancer agent. The HPV-16 E6 protein was modeled using homology modelling, with model accuracy verified through torsional angle assessment and identification of conserved regions. Molecular docking was performed to examine E6–p53 interactions. Fraction of n-hexane compounds of P. urinaria were further evaluated for their interaction with E6 by molecular docking and molecular dynamics simulation. Additionally, in vitro cytotoxicity assays were conducted using HaCaT (normal keratinocyte) and HeLa (cervical cancer) cell lines. Compounds from P. urinaria were found to interact with E6 within conserved regions and these interactions were more stable conformationally than those observed for p53. In vitro assay demonstrated that P. urinaria exhibited moderate cytotoxicity against HeLa cells but had limited toxicity toward HaCaT cells. The n-hexane fraction of P. urinaria leaves exhibits anti-cervical cancer activity by inhibiting HPV-16 E6 and eliminating cervical cancer cells.