Abstract
The Antarctic spongeDendrilla antarcticais rich in defensive terpenoids with promising antimicrobial potential. Investigation of this demosponge has resulted in the generation of a small chemical library containing diterpenoid secondary metabolites with bioactivity in an infectious disease screening campaign focused onLeishmania donovani,Plasmodium falciparum, and methicillin-resistantStaphylococcus aureus(MRSA) biofilm. In total, eleven natural products were isolated, including three new compounds designated dendrillins B-D (10-12). Chemical modification of abundant natural products led to three semisynthetic derivatives (13-15), which were also screened. Several compounds showed potency against the leishmaniasis parasite, with the natural products tetrahydroaplysulphurin-1 (4) and dendrillin B (10), as well as the semisynthetic triol15, displaying single-digit micromolar activity and low mammalian cytotoxicity. Triol15displayed the best profile against the liver-stage malaria parasites, while membranolide (5) and dendrillin C (11) were strong hits against MRSA biofilm cultures.