Structure and cytotoxic activity of sesquiterpene glycoside esters from Calendula officinalis L.: Studies on the conformation of viridiflorol

The sesquiterpene glycoside esters are responsible for cytotoxic effects of extracts of C. officinalis. Their structures were established by spectroscopic methods, chemical reactions and molecular mechanic calculations. [Display omitted] •Fifteen sesquiterpene glycosides (nine new) were isolated from a Calendula sp.•Structures were established by spectroscopic methods, chemical reactions and MM calculations.•Conflicting reports on the elucidation of alloaromadendrol epimers were clarified.•Cytotoxicity in human epithelial gastric cells was assessed by MTT and LDH assays. Topic applications of Calendula officinalis L. lipophilic extracts are used in phytotherapy to relieve skin inflammatory conditions whereas infusions are used as a remedy for gastric complaints. Such a different usage might be explained by some cytotoxicity of lipophilic extracts at gastric level but little is known about this. Therefore, we screened the CH2Cl2 extract from the flowers of C. officinalis by MTT and LDH assays in human epithelial gastric cells AGS. This bioassay-oriented approach led to the isolation of several sesquiterpene glycosides which were structurally characterized by spectroscopic measurements, chemical reactions and MM calculations. The conformational preferences of viridiflorol fucoside were established and a previously assigned stereochemistry was revised. The compounds 1a, 2a and 3f showed comparably high cytotoxicity in the MTT assays, whereas the effect on LDH release was lower. Our study provides new insights on the composition of C. officinalis extracts of medium polarity and identifies the main compounds that could be responsible for cytotoxic effects at gastric level.