Integrated In vitro, network pharmacology, and In silico analysis reveal the anti-cervical cancer properties of...

Cervical cancer remains a significant global health issue, necessitating the exploration of novel therapeutic agents. This study aims to investigate the anti-cervical cancer properties of Halimeda sp. through an integrated approach, combining in vitro assays, network pharmacology, and in silico study. The bioactivity of Halimeda sp. extracts was evaluated using DPPH radical scavenging assays and cytotoxicity against HeLa cancer cell lines. Bioactive compounds in the extracts were identified through Liquid Chromatography coupled with High-Resolution Mass Spectrometry (LC-HRMS) and assessed for their drug-likeness and toxicity. Compounds that met the specified analytical criteria were further analyzed to elucidate their mechanisms of action against cervical cancer. This investigation involved network pharmacology, molecular docking studies, and molecular dynamics simulations. The ethyl acetate extract consistently demonstrated the best activity in both DPPH scavenging analysis and cytotoxicity against HeLa cell lines. A total of 99 compounds were successfully identified in the extract, 18 of which exhibited drug-like properties and were considered relatively safe for medicinal use. A combination of network pharmacology and molecular docking analysis indicated that the anti-cervical cancer activity of Halimeda sp. extract may occur through the inhibition of PIK3R1. The compound responsible for this activity is antheraxanthin (C77). The compounds showed the strongest binding affinities among the others, with binding energies of -9.04 kcal/mol. The stability of the compound's interaction with the target protein was confirmed by the molecular dynamic simulations. This study advances knowledge of the use and development of anti-cervical cancer agents from marine algae, especially Halimeda sp.