Hyperisampsins H-M, Cytotoxic Polycyclic Polyprenylated Acylphloroglucinols from Hypericum sampsonii

Abstract

Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperisampsins H-M (1-6), were isolated from the aerial parts of Hypericum sampsonii, together with five known analogs (7-11). The structures of 1-6 were established by extensive spectroscopic analyses, including HRESIMS and NMR. In addition, the absolute configurations of these new compounds were determined by electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first examples of PPAPs possessing a unique γ-lactone ring at C-23, while 3-6 differed from normal PPAPs with an unprecedented 1,2-dioxane ring. Compounds 1-7 were evaluated for their cytotoxic activities against a panel of human cancer cell lines in vitro, of which 3, 4, and 6 exhibited significant cytotoxic activities with IC 50 values ranging from 0.56 to 3.00 μM. Moreover, compound 3 induces leukemia cell apoptotic death, evidenced by activation of caspase-3, degradation of PARP, up-regulation of Bax, and down-regulation of Bcl-2 and Bcl-xl.