Bioactivity of Spongian Diterpenoid Scaffolds from the Antarctic Sponge Dendrilla antarctica

• Published in: Marine Drugs
• Main Authors: Alexandre Bory, Andrew J. Shilling, Jessie Allen, Ala Azhari, Alison Roth, Lindsey N. Shaw, Dennis E. Kyle, John H. Adams, Charles D. Amsler, James B. McClintock, Bill J. Baker
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2020
• Subjects: diterpenoids; dendrillins; malaria; leishmaniasis; MRSA biofilm; Biology (General); QH301-705.5; Antarctic; The Antarctic; Antarc*; Antarctica
• Online Access: https://doi.org/10.3390/md18060327; https://doaj.org/article/2975797417584506a835b8f14e55d18f

The Antarctic sponge Dendrilla antarctica is 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 on Leishmania donovani , Plasmodium falciparum , and methicillin-resistant Staphylococcus 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 triol 15 , displaying single-digit micromolar activity and low mammalian cytotoxicity. Triol 15 displayed the best profile against the liver-stage malaria parasites, while membranolide ( 5 ) and dendrillin C ( 11 ) were strong hits against MRSA biofilm cultures.