Abstract
Cervical cancer remains a major global health burden, particularly in low- and middle-income countries, necessitating the discovery of novel, accessible anticancer agents. Marine macroalgae, including Halymenia durvillaei , are rich in bioactive compounds with promising therapeutic potential. H. durvillaei collected from North Sulawesi, Indonesia, was extracted with methanol and fractionated into n-hexane, chloroform, ethyl acetate, and aqueous fractions. Phytochemical profiling and cytotoxicity were assessed using the brine shrimp lethality test (15.625–1000 µg/mL) and MTT assay against HeLa cells treated with extract fractions (0.125–2 mg/mL) for 72 h. The most bioactive fraction was subjected to GC–MS characterization. Major compounds identified were evaluated through molecular docking against Vaccinia H1-related phosphatase (VHR; PDB ID: 3F81) using AutoDock Vina/CB-Dock2, followed by 100 ns molecular dynamics simulation and ADMET prediction. Phytochemical screening confirmed the presence of flavonoids (2.91 mg QE/g), alkaloids (1.03 mg/g), tannins, saponins, and steroids. The chloroform fraction exhibited the highest cytotoxicity (LC₅₀ = 33.83 µg/mL), while ethyl acetate, n-hexane, chloroform, and aqueous fractions inhibited 70–93% of HeLa cell proliferation. GC–MS analysis identified oleic acid as a major compound. In silico studies revealed stable binding of oleic acid to VHR phosphatase, a protein implicated in cervical cancer progression, supported by favorable ADMET properties. H. durvillaei demonstrates significant cytotoxic and antiproliferative activities, highlighting its potential as a source of natural anticancer agents. However, further compound isolation and mechanistic validation are required to confirm its therapeutic relevance.