Ecological and Pharmacological Activities of Polybrominated Diphenyl Ethers (PBDEs) from the Indonesian Marine Sponge Lamellodysidea herbacea

Abstract

Two known Polybrominated Diphenyl Ethers (PBDEs), 3,4,5-tribromo-2-(2′,4′-dibromophenoxy)phenol (1d) and 3,4,5,6-tetrabromo-2-(2′,4′-dibromophenoxy)phenol (2b), were isolated from the Indonesian marine sponge Lamellodysidea herbacea. The structure was confirmed using 13C chemical shift average deviation and was compared to the predicted structures and recorded chemical shifts in previous studies. We found a wide range of bioactivities from the organic crude extract, such as (1) a strong deterrence against the generalist pufferfish Canthigaster solandri, (2) potent inhibition against environmental and human pathogenic bacterial and fungal strains, and (3) the inhibition of the Hepatitis C Virus (HCV). The addition of a bromine atom into the A-ring of compound 2b resulted in higher fish feeding deterrence compared to compound 1d. On the contrary, compound 2b showed only more potent inhibition against the Gram-negative bacteria Rhodotorula glutinis (MIC 2.1 μg/mL), while compound 1d showed more powerful inhibition against the other human pathogenic bacteria and fungi. The first report of a chemical defense by compounds 1d and 2b against fish feeding and environmental relevant bacteria, especially pathogenic bacteria, might be one reason for the widespread occurrence of the shallow water sponge Lamellodysidea herbacea in Indonesia and the Indo-Pacific.

Semisynthesis and Cytotoxic Evaluation of an Ether Analogue Library Based on a Polyhalogenated Diphenyl Ether Scaffold Isolated from a Lamellodysidea Sponge

“…Compound 10: Off-white oil (7.0 mg, 55%); UV (MeOH) λ max (log ε) 283 (2.37) nm; 1 H NMR (DMSO-d 6 , 800 MHz) δ H 7.90 (1H, d, J = 2.3 Hz, H-3 ′ ), 7.65 (1H, d, J = 2.2 Hz, H-4), 7.57 (1H, d, J = 2.2 Hz, H-6), 7.41 (1H, dd, J = 8.8, 2.3 Hz, H-5 ′ ), 7.34 (1H, br d, J = 7.6 Hz, H-5 ′′ ), 7.32 (1H, dd, J = 7.6, 7.6 Hz, H-6 ′′ ), 7.09 (1H, br d, J = 7.6 Hz, H-7 ′′ ), 6.99 (1H, br s, H-3 ′′ ), 6.56 (1H, d, J = 8.8 Hz, H-6 ′ ), 5.14 (2H, s, H-1 ′′ ); 13 Hz, H-5 ′ ), 7.22 (1H, m, H-4 ′′ ), 7.20 (1H, m, H-5 ′′ ), 6.84 (1H, ddd, J = 8.7, 5.5, 3.1 Hz, H-7 ′′ ), 6.53 (1H, d, J = 8.8 Hz, H-6 ′ ), 5.17 (2H, s, H-1 ′′ ); 13…”

“…Dysideidae sponges, such as those in the genus Lamellodysidea, are known to contain a wide variety of compounds, which generally are categorized into two distinct chemotypes: those containing highly functionalized peptides and terpenoids, and those solely containing oxygenated polyhalogenated diphenyl ethers (O-PHDEs) [1,2]. It has long been understood that while the latter chemotypes are structurally similar to anthropogenic fire retardants, there is extensive evidence for their presence in sponges to be due to their antimicrobial and antifeedant activity [3][4][5][6][7]. It is now accepted knowledge that O-PHDEs are produced by symbiotic cyanobacteria within marine sponges, with the first evidence of this claim being published in 1994, where it was found that O-PHDEs from Lamellodysidea herbacea were produced by the cyanobacterial symbiont Hormoscilla spongeliae and excreted into the aqueous sponge mesophyll [2].…”

Impact of Marine Chemical Ecology Research on the Discovery and Development of New Pharmaceuticals

“…In addition to the diverse pharmacological activities, such as antimicrobial, cytotoxicity and enzyme inhibitory properties, several PBDEs have been shown to possess ecological functions [ 67 ]. Recent research by Faisal and co-workers demonstrated that 28 and 29 confer chemical defense on the sponge host against fish herbivory by the pufferfish Canthigaster solandri and on panels of environmentally relevant pathogenic and non-pathogenic bacterial strains [ 68 ]. Such ecological functions of PBDEs could explain the widespread occurrence of the sponge in Indonesia and the Indo-Pacific region.…”