Synthesis and bioactivity of tripolinolate A from Tripolium vulgare and its analogs

Abstract

A new coniferol derivative, named as tripolinolate A (1), and 11 known compounds (2-12) were isolated from whole plants of Tripolium vulgare Nees. The structure of this new compound was determined as 4-(2S-methylbutyryl)-9-acetyl-coniferol based on its NMR and HRESIMS spectral analyses. A simple and efficient method was designed to prepare tripolinolate A and its 19 analogs including nine new chemical entities for bioactive assay. Tripolinolate A and its analog 4,9-diacetyl-coniferol were found to be the two most active compounds that significantly inhibited the proliferation of different cancer cell lines with IC50 values ranging from 0.36 to 12.9μM and induced apoptosis in tumor cells. Structure-activity relationship analysis suggested that the molecular size of acyl moieties at C-4 and C-9 position might have an effect on the activity of this type of coniferol derivatives.

Keywords: Apoptosis; Compositae; Inhibition of cancer cell proliferation; Structure–activity relationship; Synthesis of tripolinolate A and analogs; Tripolinolate A; Tripolium vulgare.