Cinerascensosides A and B, Two New Cytotoxic Sulfated Saponins From the Sea Cucumber Holothuria cinerascens
Tran Thi Hong Hanh, Ninh Thi Ngoc, Le Thi Vien, Nguyen Xuan Cuong, Dao Viet Ha, Nguyen Hoai NamABSTRACT
Two new cytotoxic sulfated compounds, cinerascensosides A and B ( 1 and 2 ), alongside three described triterpene glycosides, holothurins A ( 3 ), B ( 4 ), and B 3 ( 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 (IC 50 = 2.60 µM), followed by compound 3 (IC 50 = 2.80 µM). Compound 2 displayed cytotoxicity on the KB and SK‐LU‐1 cell lines (IC 50 = 9.28 and 9.49 µM, respectively), whereas compound 3 exhibited potent activity (IC 50 = 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.