UPLC-TOF-MS/MDF oriented isolation of calonyctins K-R: Resin glycosides from Ipomoea muricata with cytotoxic and multidrug resistance reversal activities

Abstract

Eight previously undescribed resin glycosides, namely calonyctins K–R (1-8), and nine known resin glycosides (9–17), were isolated from Ipomoea muricata via the UPLC-TOF-MS/MDF guided isolation approach. The isolated resin glycosides included 25-, 27-, and 19-membered ring resin glycosides, as well as resin glycosidic acids. Notably, resin glycosides calonyctins G and H (10 and 11) exhibited considerable cytotoxicity against the A549 and HCT-116 cell lines, with calonyctin H (11) showing IC₅₀ values of 11.4 and 8.9 μM, respectively. Results of molecular docking studies indicated strong interactions between calonyctin H (11) and Sec61, suggesting that Sec61 may serve as a critical target mediating their cytotoxic effects. Additionally, calonyctins K and L (1 and 2) exhibited a dose-dependent enhancement of vincristine cytotoxicity, achieving an inhibition rate exceeding 80% in KB/VCR cells at 25 μM. The results of the in vivo evaluation of calonyctin L (2) at a dosage of 20 mg/kg demonstrated a synergistic antitumor effect with vincristine, resulting in a 60.5% inhibition rate. These findings provide valuable insights into the therapeutic potential of resin glycosides derived from I. muricata.