<div><p>Chemical investigation of the soft coral <i>Sarcophyton glaucum</i> collected from the Red Sea led to isolation of 11 isoprenoidal metabolites (<b>1</b>–<b>11</b>). A new sesquiterpenoid, 6-oxo-germacra-4(15),8,11-triene (<b>1</b>), a new natural cembranoid, sarcophinediol, along with two known sesquiterpenoids (<b>2</b> and <b>3</b>) and seven known cembranoids (<b>5</b>–<b>11</b>) was obtained. The structures of the compounds were established based on their NMR, MS, IR and UV spectral data. All compounds were evaluated for their cytotoxicity employing three cancer cell lines (HepG2, MCF-7 and HCT116). Compounds <b>4</b> and <b>6</b> showed significant cytotoxicity towards HepG2 with IC<sub>50</sub> values of 18.8 ± 0.07 and 19.9 ± 0.02 μM; respectively. Compounds <b>5</b>–<b>7</b> exhibited potent cytotoxicity against MCF-7 cells with IC<sub>50</sub> values of 9.9 ± 0.03, 2.4 ± 0.04 and 3.2 ± 0.02 μM, respectively. Compounds <b>1</b>, <b>4</b> and <b>5</b> showed significant activities towards HCT116 cells with IC<sub>50</sub> values of 29.4 ± 0.03, 19.4 ± 0.02 and 25.8 ± 0.03 μM, respectively.</p></div
