Polyprenylated Benzoylphloroglucinols Isolated from <i>Garcinia</i> Species and Their Cytotoxic Effects on Cancer Cell Lines

Polyprenylated benzoylphloroglucinols (PPBPs) make up a group of complex natural products with anticancer potentials that are mainly distributed in <i>Garcinia</i> plants. As part of our intensive exploration on new bioactive substances from this genus, we report two undescribed PPBPs, picrorhizones I (<b>1</b>) and J (<b>2</b>), along with four known analogues (<b>3</b>-<b>6</b>) from the stem bark of <i>Garcinia picrorhiza</i> and <i>Garcinia gracilis</i>. 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 <i>Garcinia</i>, 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 <i>G. gracilis</i>. The cytotoxic evaluation of the isolated compounds revealed that isogarcinol (<b>4</b>) and garciyunnanin L (<b>5</b>) significantly inhibited the growth of KB and Hela S3 cancer cells with IC₅₀ values lower than 10 μM, while <b>5</b> was also strongly active against the Hep G2 cancer cell line with an IC₅₀ 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.