Cyclodepsipeptides: Isolation from Endophytic Fungi of <i>Sarcophyton ehrenbergi</i> and Verification of Their Larvicidal Activity via In-Vitro and In-Silico Studies

<i>Culex pipiens</i> mosquitoes are vectors to many viruses and can transmit diseases such as filariasis and avian malaria. The present study evaluated the larvicidal activity of marine-derived endophytic fungi <i>Aspergillus nomius</i> and <i>Aspergillus flavus</i> from the soft coral <i>Sarcophyton ehrenbergi</i> along with two known cyclodepsipeptide compounds, scopularide A (<b>1</b>) and B (2), isolated from <i>A. flavus</i> extract, against third-instar larvae of <i>C. pipiens</i>, using distilled water as a negative control and toosenedanin as a positive control. The structures of the isolated compounds were confirmed by various spectroscopic analyses. The lethal concentrations (LC₅₀ and LC₉₀) were calculated by probit analysis. Scopularide A was the most potent after 96 h treatment, with LC₅₀ and LC₉₀ values of 58.96 and 994.31 ppm, respectively, and with 82.66% mortality at a concentration of 300 ppm. To unravel the biochemical mechanism of the tested extracts and compounds, their effects against protease, chitinase, phenoloxidases and lipase enzymes from the whole-body tissue of <i>C. pipiens</i> were evaluated after 72 h treatment at LC₅₀ dose. Superior activity was observed for <i>A. flavus</i> extract against all tested enzymes. A molecular docking study was conducted for scopularide A and B on the four tested enzymes, to further verify the observed activity. Results revealed good binding affinities for both compounds as compared to the docked ligands, mainly via a number of hydrogen bonds. This was the first study to report the isolation of endophytic fungi <i>A. flavus</i> and <i>A. nomius</i> from the marine soft coral <i>S. ehrenbergi.</i> The endophytic fungal extract of <i>A. flavus</i> was found to be a promising source for a natural larvicidal agent against <i>C. pipiens</i> populations.