Polyprenylated Benzoylphloroglucinols Isolated from Garcinia Species and Their Cytotoxic Effects on Cancer Cell Lines

Abstract

Polyprenylated benzoylphloroglucinols (PPBPs) make up a group of complex natural products with anticancer potentials that are mainly distributed in Garcinia plants. As part of our intensive exploration on new bioactive substances from this genus, we report two undescribed PPBPs, picrorhizones I (1) and J (2), along with four known analogues (3−6) from the stem bark of Garcinia picrorhiza and Garcinia gracilis. The new structures were elucidated on the basis of spectroscopic analysis, particularly 1D and 2D NMR and HRESIMS, whereas the absolute configurations were determined by a combination of ECD and NMR calculations coupled with a DP4+ probability analysis. Being the least class in genus Garcinia, picrorhizone I possesses a type-A structure with the position of a benzoyl moiety attaching to one of the bridgehead carbons of a bicyclo[3.3.1]nonane skeleton, which differs from its major type-B counterparts. This work also represents the first report on the occurrence of PPBPs in G. gracilis. The cytotoxic evaluation of the isolated compounds revealed that isogarcinol (4) and garciyunnanin L (5) significantly inhibited the growth of KB and Hela S3 cancer cells with IC 50 values lower than 10 μM, while 5 was also strongly active against the Hep G2 cancer cell line with an IC 50 value of 8.02 μM. Among the B-class derivatives bearing a lavandulyl side chain, cyclization of the moiety in the bicyclic phloroglucinol skeleton enhanced the cytotoxic properties on cancer cells.