New Cell Growth-Inhibitory Cyclohexadienone Derivatives from Hypericum calycinum L.

The crude petroleum-ether extract of the aerial parts of Hypericum calycinum L. (Guttiferae) exhibited in vitro growth-inhibitory activity against the Co-115 human colon carcinoma cell line. Bioassay-guided fractionation of this extract allowed the isolation of the cyclohexadienone derivatives 1–5 , four of which are previously undescribed compounds. The structures of the known chinesin II (1) and of 2 (hypercalin A) were established by ¹H- and ¹³C-NMR spectroscopy and were confirmed by X-ray analysis of their crystalline mixture which revealed the complete relative configuration of both compounds. The structure of 3 (hypercalin B) was elucidated by means of extensive 1D- and 2D-NMR experiments, including DQ-COSY, HETCOR and LR-HETCOR. The structure of compound 4 (hypercalin C) was established by ¹H- and ¹³C-NMR spectroscopy and confirmed by X-ray analysis to be the 3,5-dihydroxy-4-{[(1R*,2S*, 5S*)-2-hydroxy-2-methyl-5-(1-methylethenyl)cyclopentyl]methyl}-6,6-bis-(3-methylbut-2-enyl)-2-(2-methylpropanoyl)cyclohexa-2,4-dien-1-one. The structures of the higher isomeric homologues 5a/5b were deduced by comparison of their UV, ¹H-, and ¹³C-NMR spectra with those of 4 . The isolated compounds appeared to be related to chinesin I and II previously isolated from Hypericum chinense L. and were responsible for the growth-inhibitory activity of the extract against the Co-115 human carcinoma cell line. Moreover, 1/2 and 3 showed molluscicidal activity against the schistosomiasis-transmitting snail Biomphalaria glabrata.