New thymol derivatives and cytotoxic constituents from Eupatorium cannabinum subsp. asiaticum

Abstract

Eupatorium cannabinum L. subsp. asiaticum Kitam (Compositae) is a perennial herb, distributed in Himalaya, China, and Taiwan [1]. Thymol derivatives [2], sesquiterpene lactones [3], diterpenes [4], flavonoids [4], pyrrolizidine alkaloids [4], and their derivatives are widely distributed in plants of genus Eupatorium. Many of these compounds exhibit anti-inflammatory, cytotoxic, and antibacterial activities [5]. Investigation on the n-hexane-soluble fraction of the aerial part of E. cannabinum subsp. asiaticum has led to the isolation of two new thymol derivatives, cannabithymol A (1) and cannabithymol B (2), together with five known compounds, including three thymol derivatives, (E)-2-methylbut-2-enolic acid 2-(2-acetoxymethyl-oxiranyl)-5-methyl-phenyl ester (3), 8-methoxy-9-O-angeloylthymol (4), and (Z)-3-acetoxy-2-hydeoxy-2-(2-hydroxy-4-methylphenol)propyl-2-ethylbut-2-enoate (5), a benzofuran, euparin (6), and a coumarin, 2H-chromen-2-one (7). The structures of the two new compounds were determined through spectral analyses including extensive 2D NMR data. Among the isolates, (E)-2-methylbut-2-enolic acid 2-(2-acetoxymethyl-oxiranyl)-5-methyl-phenyl ester (3) exhibited cytotoxic activity, with IC50 values of 0.02 and 1.02µg/mL, respectively, against DLD-1 and CCRF-CEM cell lines.