Cytotoxic prenylated acylphloroglucinols from Hypericum annulatum

A phytochemical investigation of the aerial parts of Hypericum annulatum Moris led to the isolation of five new prenylated acylphloroglucinol derivatives hyperannulatins A-E (1-3, 5 and 7) in addition to the known hypercalyxone A (4) and 3-geranyl-1-(2'-methylpropanoyl)phloroglucinol (6). The structures were determined by 1D and 2D NMR and MS spectroscopic techniques. Compounds 1 and 2 have in their structure evgenyl group, a rare hydrocarbon side chain. The cytotoxicity of isolated compounds was established on a panel of tumor cell lines (HL-60, HL-60/DOX, MDA-MB, SKW-3 and K-562) and was determined using MTT based assays. The compounds 1 and 2 showed to be the most potent cytotoxic agents, whose IC₅₀ values against the chemosensitive cell lines ranged 3.42-5.87 μM and 1.48-8.21 μM, respectively. Noteworthy, albeit all tested compounds were less potent than podophyllotoxin their IC₅₀ values were comparable to that of the other reference drug etoposide. In some of the cell lines compounds 1 and 2 even outclassed the cytotoxicity of etoposide.