Walter Balansa, Riyanti, Jelita S. H. Hinonaung, Kirsten H. Balansa, Frets J. Rieuwpassa, Revolson A. Mege
Bromopyrrole alkaloids such as hymenialdisine (1) and debromohymenialdisine (2) are recognized as potent protein kinase inhibitors and antifoulants. Despite the urgent need for novel, eco-friendly antifoulants, research on these alkaloids remains narrow, with limited understanding of their environmental fate. This study aimed to investigate the antifouling potential of a hymenialdisine analogue, stevensine, dereplicated from the Indonesian sponge Stylissa carteri. Preliminary antimicrobial activity of the sponge extract was evaluated using disc diffusion assay. Inspired by initial antimicrobial findings, a comprehensive in-silico investigation was conducted on stevensine and its derivatives, generated via MetaTox analysis. This involved molecular docking against multiple targets: the quorum sensing receptor (QSR), glycogen synthase kinase-3β (GSK-3β), and acetylcholinesterase (AChE). Preliminary antimicrobial activity assessment demonstrated that S. carteri extract inhibited the growth of the biofilm-forming bacteria Acinetobacter baumannii and Staphylococcus aureus, suggesting broad-spectrum antifouling activity. Molecular docking of stevensine and its derivatives revealed tunable scaffolds that exhibit selective inhibition towards either GSK-3β or AChE, potent quorum sensing, and dual-or triple-target inhibition. Statistical analysis showed significant differences in interaction energies among target groups (ANOVA, p = 0.00000832), particularly between AChE and the QSR (p = 0.0000004964) and between GSK-3β and the QSR (p = 0.004177242). Most importantly, predicted ecotoxicity profiles indicated that the stevensine scaffold possesses more favorable Log Koc, BCF, and Log Kow values than commercial antifoulants, suggesting a lower bioaccumulation potential. This study provides first evidence supporting stevensine derivatives as a versatile, multi-stage antifouling agents, positioning them as promising leads for the design of ecofriendly antifoulants. © 2026 Balansa et al.
Department of Fisheries and Maritime Technology, Politeknik Negeri Nusa Utara, North Sulawesi, 95811, Indonesia; Faculty of Fisheries and Marine Science, Universitas Jenderal Soedirman, Jl. Dr. Soeparno, Central Java, Banyumas, 53122, Indonesia; Department of Health, Politeknik Negeri Nusa Utara, North Sulawesi, 95811, Indonesia; Department of Informatics Engineering, Faculty of Engineering, Universitas Sam Ratulangi, North Sulawesi, Manado, 95115, Indonesia; Biology Department, Faculty of Mathematics, Natural and Earth Sciences, Manado State University, Tondano, 95619, Indonesia