Bioactivity of Spongian Diterpenoid Scaffolds from the Antarctic Sponge Dendrilla antarctica

Abstract

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.

A Minireview on Biodiscovery in Antarctic Marine Benthic Invertebrates

“…This is a chemically rich sponge, being a prolific source of highly oxidized diterpenoids with moderate antibiotic and antifungal activities against S. aureus, E. coli, and Candida albicans (Molinski and Faulkner, 1987). Bioactivities against infectious disease models including pathogens that cause leishmaniasis, malaria, and MRSA infections were also found (Bory et al, 2020). Four more diterpenes, tetrahydroaplysulphurin-1 (Figure 1), as well as membranoids B (Figure 1), D, and G, displayed low micromolar activity against Leishmania donovani with no discernible cytotoxicity against uninfected J774A.1 cells (Shilling et al, 2020).…”

Marine Terpenoids from Polar Latitudes and Their Potential Applications in Biotechnology

“…This small but diverse collection of diterpenoids showed remarkable antibiotic properties against a range of infectious disease models. The most prominent bioactivity including membranolide (66) showed >90% eradication of MRSA biofilm at or below concentrations of 25 µg/mL, dendrillin B (71), active against L. donovani infected J774A.1 at macrophages at an IC 50 of 3.5 µM, and 76 with 100% inhibition of P. falciparum at 5 µg/mL [126]. 9,11-dihydrogracilin A (64) isolated from Dendrilla sponges collected around the same area, has also recently been shown to display immuno-modulatory and anti-inflammatory properties in human cell lines [127].…”

Antifouling Diterpenoids from the Sponge Dendrilla antarctica

“…Although marine sponges of the genus Dendrilla have a widespread geographical distribution, from polar to tropical seas, [1] they are particularly abundant in Antarctic waters, and are probably amongst the most chemically studied Antarctic benthic invertebrates. The chemistry associated with sponges of this genus is very diverse, and includes lamellarins, bastadins and other alkaloids, [2–7] as well as spongiane‐related diterpenoids and seco diterpenoids, [8–16] among other classes of compounds. However, the presence of seco and nor‐spongiane derived diterpenes seems to be restricted mainly to Antarctic species, typically to Dendrilla antarctica (although there are several publications on D. membranosa , which has recently been revised to D. antarctica ).…”

“…There is also great variability in terms of the major secondary metabolites produced at different locations by the same species. These compounds, many of them with gracilane (a nor‐seco spongiane) or aplysulphurane (seco spongiane) skeletons, [13] were tested for diverse biological activities, although in most cases their potency was not very high, except for antiparasitic activity [9,16] . In many cases, some of the terpenoids were isolated in fairly large proportions, which suggested a possible ecological role for these metabolites.…”