Novel metabolite madeirone and neomarinone extracted from Streptomyces aculeoletus as marine antibiofilm and antifouling agents

Biofouling poses a significant economic threat to various marine industries, leading to financial losses that can reach billions of euros annually. This study highlights the urgent need for effective alternatives to traditional antifouling agents, particularly following the global ban on organotin compounds. PTM-346 was isolated from sediment samples on the shores of the Madeira Archipelago, Portugal. The crude extract was fractionated using silica flash chromatography and preparative HPLC, resulting in two isolated marinone compounds: madeirone ( ), a novel marinone derivative discovered in this study, and neomarinone ( ). The antifouling activities of these compounds were tested against five marine bacterial species and the larvae of the mussel . Additionally, and environmental toxicity evaluations of madeirone ( ) and neomarinone ( ) were conducted. Madeirone ( ) demonstrated significant antibiofilm efficacy, inhibiting by up to 66%, by up to 60%, and by up to 40%. Neomarinone (2) also exhibited substantial antibiofilm activity, with inhibition rates of up to 41% against , 40% against , 56% against , 46% against C. marina, and 40% against . The growth inhibition activity at the same concentrations of these compounds remained below 20% for the respective bacteria, highlighting their effectiveness as potent antibiofilm agents without significantly affecting bacterial viability. Additionally, both compounds showed potent effects against the settlement of larvae, with EC values of 1.76 µg/mL and 0.12 µg/mL for compounds ( ) and ( ), respectively, without impairing the viability of the targeted macrofouling species. toxicity predictions and toxicity assays both support their potential for further development as antifouling agents. The newly discovered metabolite madeirone ( ) and neomarinone ( ) effectively inhibit both micro- and macrofouling. This distinct capability sets them apart from existing commercial antifouling agents and positions them as promising candidates for biofouling prevention. Consequently, these compounds represent a viable and environmentally friendly alternative for incorporation into paints, primers, varnishes, and sealants, offering significant advantages over traditional copper-based compounds.