Natural Product Research in the Australian Marine Invertebrate Dicathais orbita

Abstract

The predatory marine gastropod Dicathais orbita has been the subject of a significant amount of biological and chemical research over the past five decades. Natural products research on D. orbita includes the isolation and identification of brominated indoles and choline esters as precursors of Tyrian purple, as well as the synthesis of structural analogues, bioactivity testing, biodistributional and biosynthetic studies. Here I also report on how well these compounds conform to Lipinski’s rule of five for druglikeness and their predicted receptor binding and enzyme inhibitor activity. The composition of mycosporine-like amino acids, fatty acids and sterols has also been described in the egg masses of D. orbita. The combination of bioactive compounds produced by D. orbita is of interest for further studies in chemical ecology, as well as for future nutraceutical development. Biological insights into the life history of this species, as well as ongoing research on the gene expression, microbial symbionts and biosynthetic capabilities, should facilitate sustainable production of the bioactive compounds. Knowledge of the phylogeny of D. orbita provides an excellent platform for novel research into the evolution of brominated secondary metabolites in marine molluscs. The range of polarities in the brominated indoles produced by D. orbita has also provided an effective model system used to develop a new method for biodistributional studies. The well characterized suite of chemical reactions that generate Tyrian purple, coupled with an in depth knowledge of the ecology, anatomy and genetics of D. orbita provide a good foundation for ongoing natural products research.

Anti-Inflammatory Activity and Structure-Activity Relationships of Brominated Indoles from a Marine Mollusc

“…Liquid chromatography mass spectrometry (LC-MS) separations of the chloroform extracts confirmed the presence of brominated indoles typically found in D. orbita (Figure 1, Supplementary Figure S1) [17,22,41]. The fresh hypobranchial gland chloroform extract (Figure 1a) and the egg mass chloroform extract (Figure 1b) were dominated by 6-bromoistain (pseudomolecular ion [M + H] + m / z 226, 228; [M + Na] + m / z 248, 250, UV λ max 212, 256, 308, and 408 nm) and tyrindoleninone (pseudomolecular ion [M + H] + m / z 256, 258, UV λ max 236, 248, 274, 352, 402 nm) respectively, and contained smaller amounts of 6-bromoindole (pseudomolecular ion [M + 2H] + m / z 198, 200, UV λ max 218, 260, 290 nm) and tyriverdin (pseudomolecular ion [M + Na] + m / z 535, 537, 539; UV λ max 236, 252, 274, 352, 402, and 596 nm) (Figure S1).…”

Naturally Occurring Marine Brominated Indoles Are Aryl Hydrocarbon Receptor Ligands/Agonists

“…Nothing is known about the presence of these particular compounds in seafood or other routes of human exposure. However, other brominated indoles have been isolated from marine animals and plants 60–62 or sediment 63 and some of these have been detected in seafood or other marine products consumed by humans, including oysters 64 and fish oil supplements, 65,66 at concentrations that can approach those of anthropogenic contaminants such as mono- ortho PCBs. 65 Additional studies will be needed to better understand the potential human exposure to the suite of brominated indoles including those evaluated here.…”

6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model

“…Recently 6-bromoisatin (Figure 1) from the Australian marine mollusc Dicathais orbita has become of particular interest as a major compound of the bioactive extract from this species [5]. In a study by Edwards et al [14], semi-purified 6-bromoisatin from D .…”