Abstract
The chemical investigation of the Red Sea sponge Negombata sp. led to isolation and structure elucidation of five new ceramides N ((2S,3R,4E,8E)-1,3-dihydroxyhexacosa-4,8-dien-2-yl)pentadecanamide (1), N-((2S,3R,E)-1,3-dihydroxynonadec-4-en-2-yl)stearamide (2), N-[(2S,3R,E)-1,3 dihydroxyhexacos-4-en-2-yl]palmitamide (3), N-((2S,3R)-1,3-dihydroxydodecan-2-yl)tetradecanamide (4), N-[(2S,3S,4R)-1,3,4- trihydroxypentadecan-2-yl] palmitamide (5). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated ceramides were tested for anti-anxiety action in the elevated plus maze and the light-dark transition box. Mice given diazepam or compounds number 1, 2, 3, and 5 spent longer time in the light area of the light-dark box. However, compound 4 did not produce a similar effect. Similarly, testing anti-anxiety action in the elevated plus maze test showed that the compounds number 2, 3, and 5 or diazepam were able to prolong the open arm time %. Meanwhile, compounds 1 and 4 failed to produce a similar response. In addition, the anticonvulsant action of the ceramides was assessed employing pentylenetetrazole-induced seizures, where some ceramides prolonged the time to death due to pentylenetetrazole in vivo. In silico testing of the isolated ceramides displayed reasonable GABA receptor modulator binding at the benzodiazepines site. Ceramide 1 showed slightly stronger interaction with the GABA receptor over other ceramides which is compatible with the results of their anxiolytic activity.