Ingenane and jatrophane-type diterpenoids from Euphorbia kansui with multidrug resistance reversal activity

Bioassay-guided purification on the ethanolic extract of the roots of Euphorbia kansui Liou ex S.B.Ho (Euphorbiaceae) led to the isolation of one unreported ingenane-type (euphorksol A) and six unreported jatrophane-type (euphorksjats A-F) diterpenoids, together with twenty-five known diterpenoids. Their structures were elucidated based on extensive NMR analysis and high-resolution mass spectrometry. Euphorksol A is a rare example of an ingenane-type diterpenoid with a 6,7-expoxy fragment. All compounds were examined for cytotoxicity against adriamycin (Adr)-sensitive HepG-2 and Adr-resistant HepG-2/Adr cell lines, but none showed significant activity. Then, all isolates were evaluated for their ability to reverse multidrug resistance (MDR). 6 beta,7 beta-Epoxy-3 beta,4 beta,5 beta-trihydroxyl-20- deoxyingenol and 3,5,7,15-tetraacetoxy-9-nicotinoyloxy-14-oxojatropha-6(17),11-diene showed significant MDR reversal activity in HepG-2/Adr cells (reversal fold: RF = 186.4 and 143.8, respectively) versus the positive control verapamil (Ver, RF = 93.7). Euphorksol A and kansuinin B exhibited moderate MDR reversal activity (RF = 57.4 and 68.9, respectively). These compounds are the first ingenane-type diterpenoids reported to show MDR reversal activity, which will provide new insights toward the development of MDR regulatory agents.

Automated summary

Bioassay-guided purification of the ethanolic extract from the roots of Euphorbia kansui led to the isolation of previously unreported ingenane-type and jatrophane-type diterpenoids, as well as known diterpenoids. These compounds showed potential in reversing multidrug resistance, with particular examples demonstrating significant MDR reversal activity. This research provides new insights for the development of MDR regulatory agents.