Cinerascensosides A and B, Two New Cytotoxic Sulfated Saponins From the Sea Cucumber Holothuria cinerascens.

Two new cytotoxic sulfated compounds, cinerascensosides A and B (1 and 2), alongside three described triterpene glycosides, holothurins A (3), B (4), and B3 (5), were separated from the sea cucumber Holothuria cinerascens. Their structures and absolute configurations were established through extensive spectroscopic analysis, DP4+ probability calculation, and ECD calculations. Furthermore, probable biosynthetic pathways of 1-5 were suggested. Among them, compound 4 exhibited the most potent cytotoxicity against the HepG2 cell line (IC50 = 2.60 µM), followed by compound 3 (IC50 = 2.80 µM). Compound 2 displayed cytotoxicity on the KB and SK-LU-1 cell lines (IC50 = 9.28 and 9.49 µM, respectively), whereas compound 3 exhibited potent activity (IC50 = 2.48 and 2.98 µM). Computational analyses, including molecular docking, network pharmacology, and molecular dynamics (MDs) simulations, collectively suggest a potential mechanism of action underlying the observed cytotoxic activity.