Summary: | The cytotoxicity-bioassay-guided fractionation of the ethanol extract from the marine sponge <i>Guitarra abbotti</i>, whose 1-<i>O</i>-alkyl-<i>sn</i>-glycerol ethers (AGEs) have not been investigated so far, led to the isolation of a complex lipid fraction containing, along with previously known compounds, six new lipids of the AGE type. The composition of the AGE fraction as well as the structures of 6 new and 22 previously known compounds were established using <sup>1</sup>H and <sup>13</sup>C NMR, GC/MS, and chemical conversion methods. The new AGEs were identified as: 1-<i>O</i>-(Z-docos-15-enyl)-<i>sn</i>-glycerol (<b>1</b>), 1-<i>O</i>-(Z-docos-17-enyl)-<i>sn</i>-glycerol (<b>2</b>), 1-<i>O</i>-(Z-tricos-15-enyl)-<i>sn</i>-glycerol (<b>3</b>), 1-<i>O</i>-(Z-tricos-16-enyl)-<i>sn</i>-glycerol (<b>4</b>), 1-<i>O</i>-(Z-tricos-17-enyl)-<i>sn</i>-glycerol (<b>5</b>), and 1-<i>O</i>-(Z-tetracos-15-enyl)-<i>sn</i>-glycerol (<b>6</b>). The isolated AGEs show weak cytotoxic activity in THP-1, HL-60, HeLa, DLD-1, SNU C4, SK-MEL-28, and MDA-MB-231 human cancer cells. A further cytotoxicity analysis in JB6 P<sup>+</sup> Cl41 cells bearing mutated MAP kinase genes revealed that ERK2 and JNK1 play a cytoprotective role in the cellular response to the AGE-induced cytotoxic effects.
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