Harnessing the Ecofriendly Antifouling Potential of Agelasine Alkaloids Through MetaTox Analysis and Computational Studies
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Abstract
Agelasine alkaloids derived from marine sponges of the genus Agelas represent a promising source of antifouling compounds with potential economic and environmental benefits. Notably, agelasine D (1), agelamide D (2), epi-agelasine C (3) and agelasidine A (4) are known antifoulants. However, their ecotoxicological parameters remain unreported, raising concerns about their suitability as eco-friendly antifoulants. To address this, glucuronidated and sulfated metabolites were generated using MetaTox. Their binding affinities against acetylcholinesterase (AChE) were evaluated through molecular docking using PyRx, and ecotoxicological parameters were assessed using EPI Suite™. Compounds 1–4 exhibited strong AChE binding (−7.5 to −11.4 kcal/mol), surpassing those of AChE inhibitors such as synoxalidinones A (5) and C (6) and commercial antifoulants like seanine_211 (7) and irgarol-1501 (8). Furthermore, these compounds also displayed unfavorable toxicological profiles similar to commercial antifoulants, including high log Kow (3.78 to 5.46), BCF (3.16 to 145), BAF (138.0 to 590), and Log Koc (−0.15 to 2.18) values, with longer biotransformation half-lives (266 to 590 days), indicating potential environmental and health risks. In contrast, glucuronidated and sulfated derivatives particularly 1a, 3a, 3c-3d, 4a and 4b demonstrated stronger AChE binding (−8.0 to −12.3 kcal/mol) and significantly improved toxicological profiles, including low log Kow (−0.94 to 1.29), BCF (0.64 to 1.28), BAF (0.23 to 3.16), and shorter half-lives (0.01 to 0.17 days), with non-toxic and non-mutagenic properties. While their efficient synthesis and effectiveness in real-world applications remain to be tested, compounds 1a, 3a and 3b represent promising eco-friendly antifouling candidates.
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