Polyprenylated\nBenzoylphloroglucinols Isolated from Garcinia Species and Their Cytotoxic Effects on Cancer\nCell Lines

Polyprenylated benzoylphloroglucinols (PPBPs) make up\na group of\ncomplex natural products with anticancer potentials that are mainly\ndistributed in Garcinia plants. As\npart of our intensive exploration on new bioactive substances from\nthis genus, we report two undescribed PPBPs, picrorhizones I (<b>1</b>) and J (<b>2</b>), along with four known analogues\n(<b>3</b>–<b>6</b>) from the stem bark of Garcinia picrorhiza and Garcinia gracilis. The new structures were elucidated on the basis of spectroscopic\nanalysis, particularly 1D and 2D NMR and HRESIMS, whereas the absolute\nconfigurations were determined by a combination of ECD and NMR calculations\ncoupled with a DP4+ probability analysis. Being the least class in\ngenus Garcinia, picrorhizone I possesses\na type-A structure with the position of a benzoyl moiety attaching\nto one of the bridgehead carbons of a bicyclo[3.3.1]nonane skeleton,\nwhich differs from its major type-B counterparts. This work also represents\nthe first report on the occurrence of PPBPs in G. gracilis. The cytotoxic evaluation of the isolated compounds revealed that\nisogarcinol (<b>4</b>) and garciyunnanin L (<b>5</b>)\nsignificantly inhibited the growth of KB and Hela S3 cancer cells\nwith IC<sub>50</sub> values lower than 10 μM, while <b>5</b> was also strongly active against the Hep G2 cancer cell line with\nan IC<sub>50</sub> value of 8.02 μM. Among the B-class derivatives\nbearing a lavandulyl side chain, cyclization of the moiety in the\nbicyclic phloroglucinol skeleton enhanced the cytotoxic properties\non cancer cells.