*Article* **Antifouling Napyradiomycins from Marine-Derived Actinomycetes** *Streptomyces aculeolatus* †

### **Florbela Pereira 1, Joana R. Almeida 2, Marisa Paulino 3, Inês R. Grilo 4, Helena Macedo 3,4, Isabel Cunha 2, Rita G. Sobral 4, Vitor Vasconcelos 2,5 and Susana P. Gaudêncio 1,3,\***


Received: 6 December 2019; Accepted: 16 January 2020; Published: 18 January 2020

**Abstract:** The undesired attachment of micro and macroorganisms on water-immersed surfaces, known as marine biofouling, results in severe prevention and maintenance costs (billions €/year) for aquaculture, shipping and other industries that rely on coastal and o ff-shore infrastructures. To date, there are no sustainable, cost-e ffective and environmentally safe solutions to address this challenging phenomenon. Therefore, we investigated the antifouling activity of napyradiomycin derivatives that were isolated from actinomycetes from ocean sediments collected o ff the Madeira Archipelago. Our results revealed that napyradiomycins inhibited ≥80% of the marine biofilm-forming bacteria assayed, as well as the settlement of *Mytilus galloprovincialis* larvae (EC50 < 5 μg/ml and LC50/EC50 >15), without viability impairment. In silico prediction of toxicity end points are of the same order of magnitude of standard approved drugs and biocides. Altogether, napyradiomycins disclosed bioactivity against marine micro and macrofouling organisms, and non-toxic e ffects towards the studied species, displaying potential to be used in the development of antifouling products.

**Keywords:** marine natural products; actinomycetes; biofouling; antifouling; antibiofilm; napyradiomycins; meroterpenoids; hybrid isoprenoids; drug discovery; bioprospection
