Cytotoxic Polyketide Derivatives from the South China Sea Sponge <i>Plakortis simplex</i>

Five new polyketides, plakortoxides A (<b>1</b>) and B (<b>2</b>), simplextones C (<b>3</b>) and D (<b>4</b>), and plakorsin D (<b>5</b>), together with six known analogues (<b>6</b>–<b>11</b>) were isolated from the South China Sea sponge <i>Plakortis simplex</i>. Their structures were identified by spectroscopic and chemical methods, including NMR, MS, and IR. Experimental and calculated ECD spectra and the modified Mosher’s method were used to determine the absolute configurations. Structurally, both plakortoxides A and B feature a butenolide coupled to an epoxide moiety, while simplextones C and D consist of γ-butyrolactone and cyclopentane moieties, and plakorsin D is a furan acetic acid polyketide. The cytotoxic activities of the isolates were tested, and compounds <b>8</b>, <b>10</b>, and <b>11</b> showed potent cytotoxicity against both K562 and HeLa tumor cell lines with IC₅₀ values ranging from 0.8 to 5.3 μM. Compound <b>3</b> showed significant inhibitory activity against c-Met kinase