Cytotoxic Triterpene Glycosides from Mexican Sea Cucumber <i>Holothuria inornata</i>

Sea cucumbers (Holothuriidae) are highly valued in traditional medicine and are recognized for their diverse bioactivities, which are largely attributed to their rich triterpene glycoside content. Given that <i>Holothuria inornata</i> was chemically uncharacterized, this study describes the bioassay-guided isolation of these compounds. Nine sulfated saponins were purified, and their structures were elucidated using UPLC-QTOF/HR-ESI-MS^<i>n</i> and comprehensive NMR spectroscopy. Six new compounds were identified, including inornatosides A-C (<b>1</b>-<b>3</b>) and 22<i>R</i>-holothurin B (<b>6</b>), all possessing a holostane-type aglycone, alongside inornatosides D (<b>4</b>) and E (<b>5</b>), which feature unique aglycones. Cytotoxic assays revealed that inornatoside B (<b>2</b>) exhibited potent cytotoxic activity against human mammary adenocarcinoma (MCF-7) and human lung adenocarcinoma (SKLU-1) cell lines, with IC₅₀ values between 0.47 and 0.50 μM surpassing the efficacy of the positive control. These findings not only expand the chemical diversity of holothurins but also position <i>H. inornata</i> as a promising source of anticancer compounds.