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Biofouling poses a significant threat to fisheries and maritime sectors, capable of damaging ship hulls, mariculture facilities, and marine structures. Despite the effectiveness of tributyl tin (TBT)-based antifouling in solving biofouling problems, it threatens the marine environment and human health, necessitating the exploration of ecofriendly antifouling agents. Marine sponges have evolved unique antifouling strategies that may contain potential solutions to this problem. Hence, an epoxy resin coating enriched with powder from the sponge Agelas nakamurai underwent field testing on polyethylene nets. Analysis of variance (ANOVA) demonstrated that nets pre-treated with 100, 200, and 300 mg/mL of the epoxy resin and sponge powder mix had a significant effect on biofouling growth (P < 0.05). Post-hoc Tukey's test indicated that the 100 mg/mL treatment significantly differed from other treatments. Since the authors previously characterized and predicted the presence of agelasines A-F (1-6) and agelasidine A (7) from the same sponge using NMR/LC-MS and MS-MS annotation, the currently studied A. nakamurai contains the same molecules. Molecular docking studies identified agelasines A-F and agelasidine A as promising acetylcholinesterase (AChE) inhibitors, rivaling or surpassing the AChE specific inhibitors, such as synoxazolidinones A (8) and C (9), and the antifouling agents Seanin_211 (10) and Irgarol_1501 (11). In silico ADME-T and TEST analyses on compounds 1-11 indicated that, while agelasines A-F need further optimization, agelasidine A was the most promising compound identified as potential antifouling agent in this research. This study marks the initial step in evaluating agelasines and other marine-derived molecules as eco-friendly antifouling agents. [ABSTRACT FROM AUTHOR]