Structural Characterization and Cytotoxic Activity Evaluation of Ulvan Polysaccharides Extracted from the Green Algae <i>Ulva papenfussii</i>

Ulvan, a sulfated heteropolysaccharide with structural and functional properties of interest for various uses, was extracted from the green seaweed <i>Ulva papenfussii</i>. <i>U. papenfussii</i> is an unexplored <i>Ulva</i> species found in the South China Sea along the central coast of Vietnam. Based on dry weight, the ulvan yield was ~15% (<i>w</i>/<i>w</i>) and the ulvan had a sulfate content of 13.4 wt%. The compositional constitution encompassed L-Rhamnose (Rha<i>p</i>), D-Xylose (Xyl<i>p</i>), D-Glucuronic acid (GlcA<i>p</i>), L-Iduronic acid (IdoA<i>p</i>), D-Galactose (Gal<i>p</i>), and D-Glucose (Glc<i>p</i>) with a molar ratio of 1:0.19:0.35:0.52:0.05:0.11, respectively. The structure of ulvan was determined using High-Performance Liquid Chromatography (HPLC), Fourier Transform Infrared Spectroscopy (FT-IR), and Nuclear Magnetic Resonance spectroscopy (NMR) methods. The results showed that the extracted ulvan comprised a mixture of two different structural forms, namely (“A3s”) with the repeating disaccharide [→4)-β-D-GlcA<i>p</i>-(1→4)-α-L-Rha<i>p</i> 3S-(1→]n, and (“B3s”) with the repeating disaccharide [→4)-α-L-IdoA<i>p</i>-(1→4)-α-L-Rha<i>p</i> 3S(1→]n. The relative abundance of A3s, and B3s was 1:1.5, respectively. The potential anticarcinogenic attributes of ulvan were evaluated against a trilogy of human cancer cell lineages. Concomitantly, Quantitative Structure–Activity Relationship (QSAR) modeling was also conducted to predict potential adverse reactions stemming from pharmacological interactions. The ulvan showed significant antitumor growth activity against hepatocellular carcinoma (IC₅₀ ≈ 90 µg/mL), human breast cancer cells (IC₅₀ ≈ 85 µg/mL), and cervical cancer cells (IC₅₀ ≈ 67 µg/mL). The QSAR models demonstrated acceptable predictive power, and seven toxicity indications confirmed the safety of ulvan, warranting its candidacy for further in vivo testing and applications as a biologically active pharmaceutical source for human disease treatment.